Functional Ecology 2011, 25, 18–28
doi: 10.1111/j.1365-2435.2010.01742.x
ECOLOGICAL IMMUNOLOGY
Ecological immunology and tolerance in plants and
animals
Regina S. Baucom1* and Jacobus C. de Roode2
1
2
Department of Biological Sciences, 721 Rieveschl Hall, University of Cincinnati, Cincinnati, Ohio 45221, USA; and
Biology Department, Emory University, 1510 Clifton Road, Atlanta, Georgia 30302, USA
Summary
1. Most animal studies of ecological immunology have focused on parasite resistance: defence
mechanisms through which animals prevent infection or reduce parasite growth. Resistance
mechanisms have obvious fitness benefits by reducing the fitness losses attributed to infection.
2. Intriguingly, animal researchers have largely ignored the role of tolerance mechanisms,
through which hosts do not reduce parasite infection or growth, but alleviate the negative fitness
consequences of parasite infection or growth instead. This omission stands in sharp contrast
with the plant literature, where tolerance has been studied for decades and led to many important insights.
3. Here, we show that the plant literature has a lot to offer for understanding defence against
parasites in animals. We argue that the prevailing views on tolerance in the plant literature
should direct research on animals, and that theoretical ecological and evolutionary studies
should be built on tolerance measures that are feasible and relevant in empirical studies.
4. Studying tolerance will enhance our understanding of how animals deal with parasites in their
natural environments and may provide novel ways to combat disease.
Key-words: defence, disease, ecological immunology, herbivory, host, parasite, pathogen, reaction-norm, resistance
Introduction
Parasites form the most common life form on earth (Windsor 1998), and are increasingly seen as major drivers of
ecological and evolutionary processes (Schmid-Hempel
2009). For example, parasites have been shown to drive
host behaviour (Moore 2002) and population dynamics
(Hudson, Dobson & Newborn 1998) and have been suggested to drive the evolution of sex (Hamilton 1980). Given
the high risk of infection and the fitness reductions caused
by parasites, there should be strong selection for defence
traits that protect hosts against parasites.
Recent decades have seen the rise of the field of ‘ecological
immunology’, which is specifically aimed at understanding
how animals protect themselves against parasites given their
ecological constraints (Sheldon & Verhulst 1996; Rolff &
Siva-Jothy 2003; Sadd & Schmid-Hempel 2008; Schulenburg
et al. 2009). The inclusion of ecological thinking has been a
huge demarcation from classical immunology and has led to
the important realization that the evolution of host defence is
limited by trade-offs with other host traits, including repro*Correspondence author. E-mail: regina.baucom@uc.edu
duction and lifespan. Indeed, the main premise of ecological
immunology is that host defences are costly, and should
be employed or evolve only when costs are outweighed by
benefits.
Until recently, most studies on ecological immunology
have focused on resistance, a series of defence mechanisms by
which animals prevent infection or reduce parasite growth.
Tolerance, by comparison, is another type of defence trait
that can reduce or alleviate the reduction in fitness owing to
parasite infection, without reducing parasite infection or
growth. Although the two defence traits serve the same purpose for the host – the retention of fitness – they may have
dramatically different consequences for the ecology and evolution of hosts and parasites, since resistance directly reduces
parasite fitness, whereas tolerance does not (Boots & Bowers
1999; Roy & Kirchner 2000; Rausher 2001; Restif & Koella
2003, 2004; Miller, White & Boots 2005, 2006).
In contrast with animal scientists, plant researchers have
long recognized the importance of tolerance and have
obtained major insights into its ecology and evolution in the
past twenty years. Tolerance, as a plant defensive trait, was
initially defined in the crop science literature as the ability to
produce grain in the face of disease (Painter 1951). Since that
2010 The Authors. Functional Ecology 2010 British Ecological Society
Tolerance in plants and animals 19
time, it has become known in shorthand form as the ability to
maintain fitness while sustaining damage (Simms 2000), often
in the context of plant herbivory. Although the concept of tolerance first appeared in the literature over 100 years ago
(Cobb 1894), substantial study of this trait did not occur until
the early 1990s when it became a prevalent concept in plant
evolutionary ecology, spurred in large part by a high-impact
paper published by Fineblum & Rausher (1995).
The literature on plant tolerance is rich and varied. Within
the plant sciences, hypotheses concerning the joint evolution
of tolerance and resistance have been both theoretically and
experimentally examined. Furthermore, substantial controversies regarding the terminology (see Definitions at the end
of the article) and the measurement of tolerance have been
considered. In this review, we argue that the work on tolerance in plants can provide a framework for the study of tolerance in animals. We discuss how studies of tolerance can
contribute to our understanding of ecological immunology,
and discuss potential reasons for its neglect in the animal literature. We also provide a brief synthesis of the major controversies, solutions and topics presented by the plant literature
and focus on how these insights can be valuable to future
study of tolerance in animals. Finally, we argue that a close
collaboration between empiricists and theoreticians will be
crucial to build ecological and evolutionary predictions on
the basis of experimentally realistic tolerance measurements.
Parasite defence in animals
WHY SHOULD WE STUDY TOLERANCE IN ANIMALS?
Why should we be interested in studying tolerance in animals?
There are several important reasons. First, as demonstrated
in the plant literature, tolerance can provide a potent mechanism to protect individuals against the negative fitness consequences of parasitism. As such, studying tolerance can
provide important insights into the range of strategies that
hosts can employ to maximize fitness when faced with parasites (Råberg, Graham & Read 2009). For example, we may
predict that individuals living in groups should invest more in
defence mechanisms because of increased risk of infection
(reviewed in Rolff & Siva-Jothy 2003). If we focus our experiments entirely on resistance mechanisms, we may erroneously
conclude that there is no effect of group living on host defence
if resistance does not differ among individuals, when in fact
individuals vary in tolerance. Furthermore, without making
the distinction between resistance and tolerance, researchers
may choose to measure either parasite burden or host fitness
to study resistance. If they find variation in host fitness, they
may mistakenly conclude that there is variation in resistance;
however, it is well possible that all studied animals had similar
parasite burdens, yet suffered different levels of fitness loss
(i.e. they varied in tolerance) (Corby-Harris et al. 2007).
Secondly, a major ecological question is why there is variation in immunity, and a central answer to this question has
been that host defence is costly in terms of other life-history
traits (Sheldon & Verhulst 1996; Rolff & Siva-Jothy 2003;
Sadd & Schmid-Hempel 2008; Schulenburg et al. 2009).
Although many studies have found trade-offs between
resistance and life history traits such as longevity, reproduction, developmental time and competitive ability (Boots &
Begon 1993; Kraaijeveld & Godfray 1997; Moret & SchmidHempel 2000; Simmons & Roberts 2005; McKean et al.
2008), not all studies have found an obvious cost of resistance
(e.g. Shoemaker & Adamo 2007; Voordouw, Koella & Hurd
2008). Two potential reasons for this are that: (i) tolerance,
and not resistance, is the main defence mechanism in the species studied; and ⁄ or (ii) there is a trade-off between tolerance
and resistance. The plant literature has provided examples of
such trade-offs (Fineblum & Rausher 1995; Stowe 1998; Baucom & Mauricio 2008b), and they might be present in animals
as well (Råberg, Sim & Read 2007).
A third reason for studying tolerance is that this defence
mechanism may have different consequences than resistance
for the spread of pathogens in populations and the evolution
of parasite virulence. Although the exact epidemiological and
evolutionary consequences are as yet unclear due to a lack of
models that explicitly address the coevolution of host and
parasite (Little et al. 2010), existing models do point at some
interesting resistance-tolerance differences. For example,
models that studied host defence evolution (while not allowing parasite evolution) have suggested that hosts may evolve
polymorphism in resistance, but that tolerance mechanisms
are more likely to become fixed (Boots & Bowers 1999; Roy
& Kirchner 2000; Miller, White & Boots 2005). In these models the evolution of resistance results in a negative epidemiological feedback because resistance reduces parasite
transmission. Thus, in a population with high parasite prevalence, there is strong selection for resistance and resistant
hosts will increase in number; this then leads to a decrease in
overall parasite transmission and prevalence. Because host
resistance is assumed to be costly, the costs of resistance start
to outweigh the benefits at low parasite prevalence, and susceptible hosts may be selected for again. Tolerance, in contrast, does not reduce parasite transmission, and hence results
in a positive epidemiological feedback: tolerant hosts have a
selective advantage in the presence of parasites; because tolerant hosts do not reduce parasite transmission, parasite prevalence increases with a higher number of tolerant hosts. This
higher parasite prevalence in turn favours tolerant hosts, so
that over time all hosts should become tolerant.
Models have also suggested that tolerance – in contrast
with resistance – should not result in antagonistic coevolution
between hosts and parasites (e.g. Rausher 2001), but this may
not necessarily be true (Little et al. 2010). Thus, although the
evolution of tolerant hosts may result in commensal relationships between host and parasite (Miller, White & Boots
2006), it is important to note that such commensalism is an
expressed outcome determined by both host and parasite
together. Because host tolerance reduces the cost of parasite
virulence to parasites (by killing its host a parasite can reduce
its transmissible period: e.g. Anderson & May 1982; Bremermann & Pickering 1983; Levin 1996; Frank 1996; Mackinnon
& Read 2004; Fraser et al. 2007; De Roode, Yates & Altizer
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20 R. S. Baucom & J. C. de Roode
2008), parasites can in fact evolve greater intrinsic growth
and virulence (Restif & Koella 2003; Miller, White & Boots
2006). When infecting a non-tolerant host, the expressed virulence of such parasites would be much higher than that before
tolerance evolved (Miller, White & Boots 2006). Additionally,
tolerance is also expected to result in higher parasite prevalence, and this means that even if an individual’s probability
of dying of infection decreases, overall disease in the population may in fact increase.
Finally, it has been suggested that because resistance has
negative consequences on parasite growth and transmission
whereas tolerance does not, tolerance will be less likely to
select for parasites that overcome tolerance than resistance is
likely to select for parasites to overcome resistance. This simple notion has led some authors to speculate that treatments
focused on increasing tolerance may be evolution-proof, and
should be preferred over treatments based on resistance (Roy
& Kirchner 2000; Rausher 2001; Schneider & Ayres 2008).
However, there are two major caveats. First, this ‘evolutionproof’ concept requires that tolerance does not trade-off with
other important resistance or life-history traits. Secondly,
because tolerance increases parasite prevalence (e.g. Miller,
White & Boots 2006), such treatments may result in a greater
prevalence of multiple-genotype infections. This is important,
because many theoretical studies have suggested that multiple-genotype infections may lead to within-host competition
between parasite genotypes, and select for greater competitive
ability. Because competitively ability is assumed to correlate
with virulence, such selection may result in more virulent parasites (Nowak & May 1994; Van Baalen & Sabelis 1995;
Frank 1996; Choisy & De Roode 2010). Although empirical
studies on this topic are scarce, a few studies have now confirmed the assumed relationship between competitive ability
and virulence (De Roode et al. 2005; Ben-Ami, Mouton &
Ebert 2008).
WHAT DEFENCE MECHANISMS HAVE ANIMAL
RESEARCHERS STUDIED SO FAR?
As described in the previous section, tolerance can provide a
potent defence mechanism with important ecological and
evolutionary implications. Moreover, tolerance has been
studied and used by medical professionals for a long time.
For example, humans in specific age groups, or with specific
genetic blood genotypes (e.g. a-thalassaemia) experience different incidence and severity of malarial disease, despite having similar parasite burdens (Rogier, Commenges & Trape
1996; Wambua et al. 2006; Müller et al. 2009), and tolerancebased treatments are already in use for several diseases,
including cholera and bacterial meningitis (Schneider &
Ayres 2008). However, evolutionary ecologists have largely
neglected tolerance in animals, even though they have studied
it extensively in plants. Instead, animal researchers have studied a large number of defence mechanisms that can all be
described as resistance.
For example, theoreticians often distinguish between host
traits that reduce infection probability (qualitative resis-
tance ⁄ avoidance) or reduce parasite burdens upon infection
(quantitative resistance ⁄ recovery) (Boots & Bowers 1999;
Gandon & Michalakis 2000). These defence mechanisms can
often be modelled using a single epidemiological parameter,
without describing in-host parasite densities and immune
mechanisms. Experimentalists often compare multiple clones,
genotypes or full ⁄ half-sib families of a host in the laboratory
and define resistance as the inverse parasite burden upon
inoculation with a standardized parasite dose or genotype
(Carius, Little & Ebert 2001; De Roode & Altizer 2010).
Resistance is often measured as a genetic or immunological
mechanism (Sheldon & Verhulst 1996; Rolff & Siva-Jothy
2003; Lambrechts, Fellous & Koella 2006; Sadd & SchmidHempel 2008), but can also come in the form of specific animal behaviours (Hart 1990). Since all these mechanisms
reduce infection probability or parasite growth – rather than
alleviate the disease symptoms on the basis of a given parasite
burden – they are all examples of host resistance, not tolerance. Perhaps the only tolerance mechanism that has received
considerable attention in animals is fecundity compensation:
a series of plastic responses by which hosts can compensate
for parasite-induced damage by increasing their reproductive
effort (e.g. Michalakis 2009).
It may seem puzzling that tolerance has not been extensively considered in animal systems. One potential reason for
its neglect is that resistance may be more apparent and easier
to measure in animals than tolerance. As mentioned above,
existing theoretical models predict that the arms races
between hosts and parasites should result in a large amount of
variation in resistance; in contrast, many models predict much
less variation – if not a complete absence – in phenotypes that
are tolerant. Because it is much easier to measure variable
than fixed defence types, it may be easier to detect resistance
than tolerance (Roy & Kirchner 2000; Read, Graham &
Råberg 2008). Another potential reason that tolerance has
received less treatment in the animal literature is that its study
requires twice, or more, the number of experimental individuals as would the study of resistance (see below).
There is, however, a biologically more interesting possibility, which is that animals are fundamentally different from
plants. In particular, most animals can move freely, while
plants cannot (Walbot 1985). This has important consequences for which defences animals and plants may employ:
in particular, animals can respond to parasitic threats through
behaviour, while plants need to respond physiologically.
Anti-parasitic animal behaviours can focus on avoidance of
infection (‘avoidance’), reduced infection probability (‘prophylactic self-medication’) or reduced parasite burdens once
infected (‘therapeutic self-medication’) (Hart 1990). For
example, wood ants use a form of prophylactic self-medication, whereby they incorporate pieces of conifer resin into
their nests; resin inhibits the growth of bacteria and fungi and
protects the ants against the detrimental effects of these microorganisms (Christe et al. 2003; Chapuisat et al. 2007; Castella,
Chapuisat & Christe 2008; Castella et al. 2008). Evidence for
therapeutic self-medication is mostly based on field observations on primates ingesting plant species with anti-parasitic
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Tolerance in plants and animals 21
chemicals (Wrangham & Nishida 1983; Huffman & Seifu
1989; Huffman 1997), although recent experiments have also
shown direct evidence for self-medication in several species of
Lepidoptera (e.g. Singer, Mace & Bernays 2009). Although
some plants may utilize volatiles produced by other plants to
fend off natural enemies (Himanen et al. 2010), medication is
more likely to occur in free-moving animals.
In contrast, plants have evolved a greater capacity to regenerate tissues than animals (Walbot 1985). Animals maintain
adult stem cells and are able to induce stem cell proliferation
in differentiated cells, allowing them to regenerate tissues and
maintain homeostasis (Birnbaum & Sánchez Alvarado 2008);
and some animals (e.g. lizards and planarians) are even able
to regenerate whole body parts. Overall, however, the apical
meristem in plants provides them with greater capacity for
whole-organ regeneration, and in particular the generation of
reproductive organs from somatic cells (Walbot 1985). Thus,
plants have greater capacity to retain fitness when damaged
than animals.
Although these major plant-animal differences may indicate that tolerance is less likely to evolve in animals than
plants, this certainly does not mean tolerance is unimportant
in animals. Indeed, as mentioned above, tolerance is studied
and used by medical scientists, and a series of recent studies
by evolutionary ecologists also demonstrates that tolerance
occurs in animal systems (Corby-Harris et al. 2007; Råberg,
Sim & Read 2007; Ayres, Freitag & Schneider 2008; Ayres &
Schneider 2009; De Roode & Altizer 2010). Before dealing
with the significance of these studies, we will turn to the plant
literature to learn how plant insights can be used to advance
our understanding of tolerance in animals.
Tolerance in the plant ecological literature
HOW TO DEFINE TOLERANCE AND THE BEST PRACTICE
OF ESTIMATING TOLERANCE
The term tolerance has been used loosely across plant sub-disciplines as the ability to ‘cope’ with various stresses such as
herbicide, salinity, drought or heavy metals. In the evolutionary ecology literature, tolerance is often defined as a plant
defence trait that results in the retention of fitness following
damage, whether that damage is incurred by biotic sources
such as herbivores or parasites, or abiotic sources such as herbicide or drought. Tolerance is often graphically depicted as a
reaction norm of fitness across a gradient of increasing damage, and as such it is a phenotypically plastic trait (Stowe
et al. 2000). This definition underscores how one measures
tolerance: experimental individuals are first classified by their
genetic relationships into groups, e.g. members of a family or
members of a population, the fitness of these groups is then
assayed at different levels of damage, and the estimate of tolerance for each group is subsequently described as the slope
of a line representing the relationship between fitness and
damage (Fig. 1a).
There are important considerations to take into account at
each step in the process of estimating tolerance, and such
(a)
(b)
Fig. 1. A graphical depiction of tolerance according to the plant
literature. (a) The reaction norm approach to estimating tolerance,
where the slope of the line represents the level of tolerance to damage
(in this case herbivory). (b) Reaction norms of three genotypes, showing variation within the population for tolerance, with genotype C
exhibiting a nonlinear relationship between fitness and damage.
Genotype A is less tolerant to damage then genotype B, as the slope
of the line representing tolerance is steeper for genotype A than B,
representing more change in fitness per unit of damage.
considerations will necessarily change according to the limitations of the study system being considered. Take, for example,
the first step, in which one classifies individuals into a group
according to their relatedness. If the appropriate crosses have
been performed among individuals in a greenhouse, common
garden or laboratory environment, the estimate of tolerance
can reasonably be considered to reflect a genetic component,
although variation in the study population cannot be
assumed unless the response of families or sibships are seen to
differ (Fig. 1b). It is thus important to understand the relationship of individuals within a group so that the evolutionary potential of the trait can be assessed. Some study systems
preclude the use of generated family lines – long-lived organisms such as trees, or animals that are impossible to rear in
the laboratory setting. In these situations, individuals from a
population can contribute to a population-level estimate of
tolerance, or an investigator can assess tolerance at the species
level. However, if tolerance is determined at these levels of
biological organization, the estimates will be influenced by
non-genetic sources of variation, such as environmental
maternal and population effects, and thus the evolutionary
potential of the trait cannot be clearly assessed.
The second step of estimating tolerance requires that the
fitness of replicates of these groups be assayed in more than
2010 The Authors. Functional Ecology 2010 British Ecological Society, Functional Ecology, 25, 18–28
22 R. S. Baucom & J. C. de Roode
one level of the damaging environment (Stowe et al. 2000).
This is important for two practical reasons: first, a single individual cannot be both damaged and non-damaged, and secondly, if fitness were measured in only a single environment,
and then compared among genetic lines, one cannot be certain that a differential response in fitness between lines is a
consequence of the environmental factor in question or a
consequence of an unknown environmental factor (Simms
2000). Furthermore, if fitness in only one environment were
considered, it would not be possible to determine if fitness
differences between lines were due to tolerance to the environmental factor in question, or due to differences in general vigour, which is defined as a genotype’s ability to perform well in
response to all unexamined environmental factors (see Simms
2000 for a thorough discussion). Thus, tolerance is not a trait
that is as easily scored as many other traits. Because of the
need to measure fitness in multiple environments, an assessment of tolerance will require double the number of experimental individuals as would, for example, resistance, or the
measure of a simple phenotype. This could present an obstacle to a researcher who works on organisms that are not easily
reared and maintained in the laboratory setting, as in the previous example.
Finally, the operational estimate of tolerance is commonly
made in one of two ways: an estimate of the slope in a reaction
norm, as previously discussed and depicted in Fig. 1, or as the
difference in average fitness of replicates grown in a damage
environment compared to fitness in a control environment
(point tolerance; Wd ) Wu). The latter estimate of tolerance
is generally used when damage is measured categorically,
such as when estimating tolerance given the presence ⁄ absence
of herbicide or other abiotic agent (Baucom & Mauricio
2004, 2008a,b), or when using a specific level of imposed damage, such as the removal of a certain amount of leaf tissue
from all individuals within the treatment environment (Tiffin
& Rausher 1999). The former is most often used when damage can be scored as a continuous variable – for example, the
amount of leaf material removed by insects in the field (Mauricio, Rausher & Burdick 1997). A major difference between
the two common operational estimates of tolerance is that the
reaction norm approach can identify potential nonlinear
components of tolerance, e.g. some families overcompensate
at low levels of damage yet decrease in fitness at higher levels
of damage, whereas point tolerance will not elucidate this
type of relationship between fitness and damage.
How each researcher operationalizes tolerance is dependent upon the study system in question, and specifically, the
agent of damage under investigation. For example, if a
researcher wishes to assess tolerance to parasitism in a wildcaught, natural population of mice, it makes sense to use the
reaction norm approach, in that the amount of parasites present in a sample derived from stomach contents or blood is
quantified rather than experimentally imposed, and the fitness of these individuals is regressed across this gradient of
increasing ‘parasite load’ or ‘burden’ (see Definitions). Of
course, this is dependent on the researcher’s ability to score
the fitness of said mice, as well.
As discussed previously, the measure of tolerance in the
above scenario would be restricted to a population level estimate, unless the researcher can assess fine-scale relatedness in a
group of wild-caught organisms. It is possible that in some
study systems, the genetic relatedness of individuals could be
determined by the use of genetic markers, such that one might
be able to determine which wild-caught individuals were members of the same sib-ship. Using the previous example of wildcaught mice, a researcher would need to accurately measure
the naturally occurring parasite load within each wild-caught
individual, determine the relationship of each individual to
one another, and make an accurate assessment of the number
of offspring each parent produced, either by counting the number of offspring in a den, or again by the use of genetic markers.
However, the feasibility of this untested idea rests on the ability
to correctly identify the relatedness among individuals in a
population to the level of a sibship and is best attempted in
organisms that do not move far from their natal home site.
Thus, in many situations it may be most feasible to measure
tolerance on organisms that can be reared in the lab, with damage being experimentally imposed rather than natural.
ISSUES PERTINENT TO THE ESTIMATION OF
TOLERANCE
There are important considerations pertinent to the estimation of tolerance that have been discussed in the plant literature that are relevant to studies of tolerance across systems,
namely, biases inherent to the use of natural or artificial damage, how fitness should be measured, and the importance of
controlling for differences in the scale of measurement
between fitness and damage. Each of the above can obscure
or alter an assessment of variability in tolerance in the study
population and ⁄ or affect the ability to accurately compare
the level of tolerance across species and experiments.
The discussion in the plant literature of whether one should
use natural vs. artificial damage has centred on damage via
insect herbivory. Tiffin & Inouye (2000) statistically described
the benefits and costs of using experimentally imposed vs.
natural damage, concluding that artificial damage results in a
more accurate estimate of tolerance, but the use of natural
damage leads to more precise estimates, or estimates that
have a higher degree of experimental reproducibility. They
suggest the biases resulting from either the use of experimental or natural damage should be considered in light of the
main goal of the experiment. For example, if one wishes to
produce tolerance estimates that are closer to the real value of
tolerance, one should impose artificial damage, and if an
assessment of genetic variation in tolerance, fitness costs of
tolerance, or selection is of interest, then the use of natural
damage will produce greater precision of underlying estimates. This is because the presence of genetic variation in a
study population is determined by an ANOVA, and if the precision behind the estimate of tolerance is biased, so too will be
the model’s residuals and the power to detect differences
among families. Lehtilä (2003) disagreed with their conclusions, stating that an assumption of Tiffin and Inouye’s
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Tolerance in plants and animals 23
statistical model – that of an equal distribution of levels of
herbivory among natural and artificial damage – was unrealistic, and that the use of a carefully controlled allocation of
imposed damage among experimental individuals by the
researcher would lead to both more accurate and precise estimate of tolerance. Inouye & Tiffin (2003) made the compelling case that this concern was more relevant to situations in
which the distribution of damage across experimental individuals approximated the mean level of damage in the population, but was not as relevant to experiments in which damage
exhibited a bimodal distribution, or one in which the distribution of herbivory does not concentrate closely to the mean
level of herbivory in the population. This discussion is relevant to future research in that some study systems, for various
reasons, might preclude assessment of naturally occurring
damage and require the use of artificially imposed damage.
Thus, this discussion should be helpful in guiding experimental design decisions, as it is applicable to studies investigating
tolerance to parasitism, or tolerance to any agent of damage
that might vary in a density-dependent manner.
Various authors have discussed or experimentally determined the influence that the measure of fitness might have on
tolerance (Strauss & Agrawal 1999). The majority of plant
studies use seed production as the estimate of fitness, which is
a measure of female plant fitness and is distinct from the estimate of male plant fitness, or the number of seeds sired
through pollen donation. Few studies have simultaneously
considered tolerance based on female and male estimates of
fitness. In some cases tolerance varies according to sex, yet in
other systems it does not (Ashman, Cole & Bradburn 2004;
Stephenson et al. 2004; Cole & Ashman 2005). How the sexes
allocate resources to tolerance is still a relatively unexplored
concept in studies of plant tolerance, and is as yet virtually
unexamined in animal systems. Furthermore, in many study
systems it will be difficult to measure fitness as reproductive
output, and fitness correlates, such as biomass allocation, longevity or other measures might be used instead. In such situations it is important to initially identify the strength of the
relationship between reproductive output and the measure
used, and to recognize the limitations inherent to using them.
Finally, another methodological concern was examined by
Wise & Carr (2008) in which the necessity of using the same
scale of measurement between fitness and damage when measuring tolerance was demonstrated. For example, when quantifying the amount of damage as a proportion of the total
plant, fitness should also be on the ‘multiplicative’ scale, in
their example, the natural log of fitness. Using an additive scale
for one trait, such as the number of seeds per plant, and a multiplicative scale for the other, such as the proportion of damage,
can lead to the aberrant conclusion that variability for tolerance is present in the study population, when in fact it is not.
MAJOR HYPOTHESES ADDRESSED IN THE PLANT
LITERATURE
Many questions concerning the evolution of tolerance have
been addressed in the plant literature, from the factors that
maintain tolerance, to the effect of competition on the expression of costs of tolerance, to the potential for ontogenetic
changes in the level of tolerance. A discussion of all of the theoretical and experimental treatments concerning plant tolerance would require its own review, and for this reason we list
some of the main hypotheses that have been addressed in
Table 1, although the list and its references are by no means
exhaustive. Below, we discuss a predominant focus of questions concerning tolerance studied in plant systems – the
potential factors responsible for the maintenance of tolerance.
Questions concerning the maintenance of tolerance have
derived from the oft-made observation that variation for tolerance exists within populations of many different study systems. This finding has intrigued plant biologists, as the
general thought on the basis of existing models is that all individuals should be highly tolerant following the action of selection (see above). To explain this apparent paradox between
expectations and empirical observations, researchers have
suggested that the presence of allocation costs, or fitness
costs, might be working to maintain the level of tolerance at
intermediate values, as might correlations between tolerance
and other traits, namely, resistance (Núñez-Farfán, Fornoni
& Valverde 2007).
A review of the plant evolutionary ecology literature finds
that fitness costs associated with tolerance are widely empirically supported, suggesting that this type of cost can act to
maintain intermediate levels of tolerance in a population
(Tiffin & Rausher 1999; Fornoni et al. 2004). However, costs
in the form of a negative correlation between resistance and
tolerance are less supported, with the majority of systems
finding instead a pattern of simultaneous allocation to both
forms of defence (Núñez-Farfán, Fornoni & Valverde 2007;
but see Fineblum & Rausher 1995; Stowe 1998; Baucom &
Mauricio 2008a,b). An alternative to the hypothesis that a
correlation between tolerance and resistance maintains tolerance at an intermediate level has been the suggestion that
stabilizing selection, due to a nonlinear cost or benefit as a
function of allocation to defence (Tiffin & Rausher 1999) acts
to maintain tolerance and ⁄ or other defensive traits; however,
the empirical work finds mixed support for this idea (NúñezFarfán, Fornoni & Valverde 2007). Although the potential
for costs of tolerance has been assessed in many dicot plants
(Núñez-Farfán, Fornoni & Valverde 2007), these concepts
are relatively unexplored in animal systems, with the exception of malaria-infected mice, which exhibited a negative
relationship between resistance and tolerance, and thus a cost
of tolerance and potential constraint on its evolution
(Råberg, Sim & Read 2007).
Applying plant insights to studying tolerance in
animals
How can animal researchers take advantage of this long
history of measuring tolerance in plants? A fruitful approach
would be to adopt the most widely accepted method from
the plant literature – the reaction norm approach (Simms
2010 The Authors. Functional Ecology 2010 British Ecological Society, Functional Ecology, 25, 18–28
24 R. S. Baucom & J. C. de Roode
Table 1. Various questions concerning tolerance that have been addressed in the plant literature
Hypothesis or general aim of study
Conclusion
References
Does tolerance vary among populations?
Yes, although this result might differ among species
Does tolerance change with ontogeny?
Tolerance is high in early stages of a plant’s life,
declines in seedling states yet increases toward
reproductive age; exceptions to this uncovered in
Cucurbita spp.
Costs of tolerance to deer herbivory dependent on
the presence of insects
Increased photosynthetic rate and branching, high
relative growth rates, high levels of carbon storage
in roots, etc
The conclusions differ according to the species
assayed
Juenger, Lennartsson & Tuomi
2000; Fornoni, Valverde &
Núñez-Farfán 2004; Baucom &
Mauricio 2008a,b
refs in Boege & Marquis 2005; Du
et al. 2008
Do costs of tolerance change according to
the community context?
What are the mechanisms of tolerance?
Does the expression of tolerance or costs
of tolerance vary with nutrient level?
Can tolerance traits promote mutualisms?
Do costs of tolerance change according to
competitive environment?
Can tolerance traits impose selection on
herbivores?
Are there QTL associated with tolerance
traits?
Are invasive populations of a species more
tolerant of damage?
Is there a quantitative genetic basis for
tolerance?
What is the relationship between vigor
and tolerance?
Enhancing mutualisms may offset fitness costs of
damage and thus be a mechanism of tolerance
Costs of tolerance found to be significant when
plants grown in absence, but not presence, of
competition
Suggested by Stinchcombe in 2002, but not borne
out in a study of Datura and a specialist leaf beetle
Genetic variation for tolerance yet no significant
QTL detected
Invasive populations of Chinese tallow tree are more
tolerant of herbivory
Additive genetic variation for either tolerance or
tolerance traits documented
Fundamental growth rules underlying vigor have
constitutive effects on tolerance
2000) – and apply this directly to animals. This was indeed
done by Råberg, Sim & Read (2007), who studied tolerance
in a system of laboratory mice and the rodent malaria parasite
Plasmodium chabaudi. They infected five strains of mice with
three clones of the parasite and showed that mouse strains
varied in both average parasite burden (i.e. variation in resistance) and in the slope of the relationship between disease
severity and parasite burden (i.e. variation in tolerance). The
researchers explicitly included uninfected mice in this analysis, to provide the controlled level of ‘no damage’ into their
reaction norm estimation (Fig. 2a).
Other studies have used different ways to measure tolerance in their animal systems. For example, a study on parasites of monarch butterflies found host family specific
intercepts for the relationship between host life span and parasite load among infected butterflies (Fig. 2b), and described
this as variation in tolerance (de Roode & Altizier 2010); in
this case the authors justified the use of different intercepts
(instead of different slopes) among infected animals because
uninfected animals (with sporeload 0) did not differ in host
life span and were not included in the analysis of the relationship between lifespan and parasite load. Yet other studies
have defined tolerance as the ability to survive infection given
a certain parasite load. For example, Corby-Harris et al.
(2007) infected 11 inbred lines of Drosophila melanogaster
with the bacterium Pseudomonas aeruginosa, and measured
Stinchcombe 2002a; Stinchcombe
& Rausher 2002
Refs in Strauss & Agrawal 1999;
Tiffin 2000
Hochwender, Marquis & Stowe
2000; Stevens, Waller & Lindroth
2007
Strauss & Murch 2004; Oliver,
Leather & Cook 2009
Siemens et al. 2003
Stinchcombe 2002b; Espinosa &
Fornoni 2006
Weinig, Stinchcombe & Schmitt
2003
Zou et al. 2008
Juenger & Bergelson 2000; Fornoni,
Valverde & Núñez-Farfán 2003
Weis, Simms & Hochberg 2000
both bacterial load and the ability to survive infection over
47 h post-infection. They found variation in both of these
measures; however, the measures were not correlated, demonstrating that lower parasite loads did not necessarily result in
greater survival, and thereby suggesting variation in tolerance
(Fig. 2c). Similarly, a number of other studies on Drosophila
infected with bacterial strains also showed varying mortality
rates for given bacterial loads (Dionne et al. 2006; Ayres, Freitag & Schneider 2008; Ramsden, Cheung & Seroude 2008;
Ayres & Schneider 2009).
What is clear from these examples is that different definitions of tolerance have already been employed in the animal
literature. This is regrettable, as it may lead to the erroneous
conclusion that one is studying tolerance when in fact one is
not; it could also lead to the inability to draw comparisons
among tolerance studies in animals. We suggest that researchers take advantage of the reaction norm approach outlined
above, and in so doing consider three important points when
attempting to estimate tolerance: (i) can fitness be adequately
characterized; (ii) can more than one level of parasite burden
be estimated or imposed; and (iii) what level of replication
can the researcher practically employ, i.e. replicates of a family or genetic line, or replication at the population or species
level?
While we acknowledge that each study system will present
its own practical limitations, thus precluding a ‘one size fits
2010 The Authors. Functional Ecology 2010 British Ecological Society, Functional Ecology, 25, 18–28
Tolerance in plants and animals 25
(a)
(b)
(c)
all’ approach to estimating tolerance, we again stress the
importance of accurately capturing each component of the
tolerance reaction norm. First and foremost, it is important
that an adequate proxy of reproductive output be employed,
since by definition tolerance is the ability to maintain fitness
following damage. In the above examples of tolerance in animals, measures of disease severity, longevity or survivability
were being used as a measure of reproductive output. How
well these measures reflect tolerance, as it is currently defined,
will depend on the strength of their correlation to fitness. The
fitness proxy chosen by an investigator will likely vary according to the study system, and will require preliminary investigations or prior knowledge as to its suitability. Furthermore,
and as previously stated, the measurement of damage will be
dependent on the study system in question. In the plant herbivory literature, damage is generally estimated as the
amount of leaf material removed via feeding by an herbivore
(Strauss & Agrawal 1999). Investigations of tolerance to plant
parasitism report damage as a percentage of the total plant
exhibiting symptoms of disease, or in a case of systemic infection, the number of aeciospores of a rust fungus (Roy et al.
2000). In the animal work described above, tolerance is estimated on the basis of parasite load or burden, not damage
(Definitions): this different measure makes a lot of sense when
studying host-parasite coevolution, since there will be different evolutionary consequences depending on whether host
defences directly reduce parasite fitness or not (Little et al.
2010).
WHERE THEORY AND EMPIRICISM NEED TO MEET
Fig. 2. Three measures of tolerance so far employed in the animal
literature. (a) Råberg, Sim & Read (2007) used the reaction norm
approach to analyse variation in tolerance among laboratory mouse
strains infected with the rodent malaria parasite Plasmodium chabaudi. They demonstrated different slopes of the relationship between a
fitness measure (in this case minimum red blood cell density) and parasite load (in this case peak parasite density) as variation in tolerance.
This approach specifically includes a zero-value of parasite load (i.e.
uninfected control animals) to determine the shape of the reaction
norm. (b) De Roode & Altizer (2010) found different y-intercepts of
the relationship between a host fitness measure (monarch adult longevity) and parasite load among family lines of the monarch butterfly
(Danaus plexippus) infected with the protozoan Ophryocystis elektroscirrha. They defined these intercept differences among infected
animals as variation in tolerance; they did this because there were no
significant differences among the longevity of uninfected monarchs
(with sporeload 0); hence the intercept of the sporeload-lifespan relationships excluding the 0 sporeload animals should reflect tolerance,
not vigor. (c) Corby-Harris et al. (2007) infected strains of Drosophila
melanogaster with a standard dose of Pseudomonas aeruginosa, and
determined fly survival for 47 h post-infection. They found no relationship between fly survival hazard ratio and bacterial load, suggesting that fly strains with similar bacterial loads have different risks of
dying of infection (i.e. variation in tolerance). Note that data presented in a, b and c are not the real data from these studies, but data
made up to closely resemble real patterns and to clearly show the different tolerance measurements used. Note that data points in a and b
represent host individuals, whereas data points in c represent fly strain
means.
A major challenge in understanding the epidemiological consequences of tolerance will be to develop theory that is based
on empirically feasible measures of tolerance. Most current
theoretical models follow variations on classical susceptibleinfected-resistant (SIR) epidemiological models (Anderson &
May 1992). In these models, hosts move between susceptible,
infected and recovered compartments, and are born and die
on the basis of rate constants, including a transmission rate b,
a parasite-induced mortality rate (virulence) a and a host
recovery rate c. In these models increased resistance can
be modelled as a reduced b (Boots & Bowers 1999; Restif
& Koella 2003) or increased c (Boots & Bowers 1999; Restif
& Koella 2003; Miller, White & Boots 2005; Best, White &
Boots 2008) while increased tolerance can be modelled as a
decreased a (Boots & Bowers 1999; Restif & Koella 2003;
Miller, White & Boots 2005; Best, White & Boots 2008).
Slightly different models have expressed tolerance as a reduction in host longevity (Roy & Kirchner 2000), or a smaller
reduction of host fecundity (Restif & Koella 2004).
An important point is that most of these models do not
explicitly model within-host parasite burdens, and simply
assume that rate parameters are the same for each infected
host within a class (e.g. tolerant vs. non-tolerant hosts). Thus,
these models implicitly measure tolerance as a reduced parasite-induced mortality rate of infected host individuals, rather
than a reaction norm of fitness as a function of parasite load.
2010 The Authors. Functional Ecology 2010 British Ecological Society, Functional Ecology, 25, 18–28
26 R. S. Baucom & J. C. de Roode
Where within-host parasite burdens have been modelled
(Miller, White & Boots 2005), it has been shown that the exact
shape of the relationship between parasite burden and virulence (and hence tolerance) crucially affects the evolutionary
trajectory of parasite virulence evolution.
Thus, although decades of plant research have concluded
that reaction norms are the best approach to measure tolerance, our current theory is based on different parameters,
which are difficult to measure in natural systems. Therefore,
in order to enhance our understanding of tolerance in animal
systems, it is essential to develop theory based on measurable
tolerance mechanisms, and to measure tolerance in ways that
are relevant to theory. Without such synergy, the study of
host tolerance may become as problematic as the study of
virulence evolution, which has also suffered from the fact
that simple theoretical assumptions have been difficult to test
in real-life systems (Ebert & Bull 2003; De Roode, Yates &
Altizer 2008).
Conclusions
As is clear from this review, tolerance has been intensively
studied in plants over the last few decades. These studies have
shown that tolerance can provide a potent mechanism against
natural enemies and that it plays a significant role in the ecology and evolution of plants. The rich literature on plant tolerance also provides clear guidelines on how to best measure
tolerance in animals. In particular, plant studies agree that: (i)
adequate measures of fitness should be measured; (ii) more
than one level of damage or parasite burden should be estimated or imposed; and (iii) genetic replicates of host families
will provide the best estimate of genetic variation in tolerance.
Animal studies have so far mostly focused on resistance
mechanisms, and the role of tolerance remains poorly understood. Studies of tolerance in animals will be necessary to
obtain a better understanding of the full range of parasite
defence mechanisms that animals employ, and will have relevance for at least three reasons. First, such studies will provide
insight into the relative role of tolerance in animals and plants.
For instance, it is possible that tolerance is much less important and prevalent in animals than in plants, because most
animals are mobile and can use behavioural in addition to
physiological defence mechanisms. Secondly, tolerance studies will provide insights into how ecological and life-history
constraints drive the evolution of defence: by exclusively
focusing on resistance, important insights may be lost. Finally,
tolerance studies in animals may result in new ways to combat
disease in livestock and humans. Indeed, theory has suggested
that tolerance mechanisms may be less prone to counterevolution of pathogens and thereby more sustainable.
Although plant studies provide a good starting point for
studying tolerance in animals, we have also shown that the
measure of tolerance used in the plant literature is not the
same as that used in theoretical models. Thus, a proper synergy between theoretical and empirical studies will be
required, in which theoretical studies are built on tolerance
measures that are feasibly measured in experimental systems.
Without such synergy, it will be hard to make long-term ecological and evolutionary predictions on the basis of singlegeneration laboratory experiments.
Acknowledgements
The authors wish to thank D. Ardia, A. Graham, D. Hawley, T. Lefèvre, T.
Little, L. Martin, A. Read and an anonymous reviewer for critically reviewing a
previous version of this manuscript.
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Definitions
Defense. We use defence to widely denote mechanisms that
protect the host against fitness loss induced by natural enemies (e.g. herbivores and parasites) or abiotic factors.
Resistance and tolerance in studies of herbivores and abiotic
factors. In studies of herbivory and abiotic factors such as
pesticides, resistance is defined as the ability to prevent or
reduce damage caused by herbivores or abiotic factors; tolerance is defined as the ability to maintain fitness in the presence
of incurred damage – often measured as the percent of leaf
area or biomass removed by herbivores, abiotic factors or
experimentalists.
Resistance and tolerance in studies of parasites. Resistance
against parasitism is defined as the ability to prevent infection
(qualitative resistance) or to reduce parasite growth and burdens upon infection (quantitative resistance). Tolerance
against parasitism is defined as the ability to maintain fitness
in the presence of infection – often quantified as parasite load
or burden. Thus, resistance directly reduces the fitness of the
parasite. In contrast, tolerance does not directly affect the
parasite, but instead alleviates the fitness loss caused by the
parasite. Note also that in order to study tolerance, parasite
studies investigate the relationship between parasite load and
fitness (Fig. 2a), while herbivore and abiotic studies analyse
the relationship between damage and fitness (Fig. 1). Thus,
implicit in the estimate of tolerance to parasites is that parasites cause damage to the host, and that higher parasite burdens result in greater damage. Moreover, the use of parasite
burdens makes sense from the point of view of studying
coevolution of hosts and parasites, assuming that reductions
in parasite load reduce parasite transmission.
Parasite. We define parasites as organisms that reduce the
fitness of their host. This definition includes viruses, bacteria,
fungi, worms, ecto-parasites and parasitic plants.
Virulence. Following the animal literature, we define
virulence as parasite-induced reductions in host fitness. Note
that this is a distinctly different definition than used in the
plant literature, in which virulence is defined as a parasite’s
infectivity.
Parasite burden. Parasite burden is defined as the number
of parasites within a host. Higher burdens may result from
higher initial infectious doses or higher parasite growth.
Received 11 February 2010; accepted 1 June 2010
Handling Editor: Dana Hawley
2010 The Authors. Functional Ecology 2010 British Ecological Society, Functional Ecology, 25, 18–28