Immune modulation by Teladorsagia circumcincta and implications
for control
Tom N McNeilly
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik,
Midlothian, UK. EH26 OPZ
Teladorsagia circumcincta is the primary cause of parasitic gastroenteritis in small
ruminants in temperate regions. Immunity to this parasite is slow to develop,
requiring continuous exposure over a number of weeks. This is consistent with an
ability of the parasite to suppress host immune responses.
We are now beginning to unravel the mechanisms and molecules this parasite uses
to manipulate host immunity. For example, we know that Foxp3+ regulatory T cells
are recruited to the gastric mucosa during infection the parasite induces an early
regulatory immune response which is partially overcome during more chronic
infection. Furthermore, excretory-secretory (ES) products derived from fourth stage
larvae (L4), the parasitic stage most targeted by the immune response, are
profoundly suppressive of T cell activation and this is in part mediated by the
regulatory cytokine interleukin-10. Proteomic analyses of L4 ES products have
identified fractions highly enriched for suppressive activity, although attempts to
identify the specific suppressive molecules within these fractions have been largely
unrewarding. Detailed proteomic and transcriptional analysis of L4 parasites within
either the mucosa or the lumen of the abomasum has been more successful: this
approach has identified a number of potentially immunosuppressive molecules which
are enriched in mucosal-dwelling L4, including TcK6, an ShK-domain containing
protein which inhibits cytokine production by T cells, and thioredoxin peroxidase, an
antioxidant with the potential to modulate macrophage function. Current work is now
focused on testing these molecules as vaccine antigens, with the aim of inducing
antibodies to neutralize their suppressive effects and thus enhance parasite-induced
immunity.