Mechanisms of innate defense against infection of the lung

CIHR-UBC Strategic Training Program for
Translational Research in Infectious Diseases
Address: D452 – 2733 Heather Pavilion, Vancouver, BC V5Z 3J5
Voice: (604) 875-5063 Fax: (604) 875-4013 Website:
Research Theme:
Molecular pathogenesis, innate immunity, cell signalling, immunomodulation
Mechanisms of innate defense against infection of the lung
Principal Investigator:
Dr. David P. Speert, MD
The normal lung is exposed to about 20,000 liters of air per day, but the frequency of serious lower respiratory tract
infection is very uncommon. However, certain groups of patients, such as those with cystic fibrosis experience frequent
and chronic bacterial infection. The purpose of research in this laboratory is to gain a clearer understanding of the
nature of innate defenses of the lung against bacterial infection. To achieve this goal, the host-bacterial interaction in the
CF lung is being explored. Studies focus on both bacterial pathogenesis and host defense mechanisms, but all research
is concentrated at the interface between host and pathogen. The following studies are ongoing:
Studies of the molecular epidemiology of bacterial infection in CF and in other pediatric infectious diseases. These
studies involve genetic fingerprinting of bacterial isolates using various methods and deducing the likelihood of
patient-to-patient spread.
Studies on biofilm formation and quorum sensing by bacteria from the Burkholderia cepacia complex.
Studies on the role of macrophages, neutrophils and dendritic cells in defense of the lung against infection with
Pseudomonas aeruginosa and B. cepacia.
Identification of the bacterial determinants which prevent microbial clearance from the lung of normal and
compromised mice.
Characterization at the molecular level of novel immunodeficiency disorders.
Development of a novel antiinfective agent for use in patients with cystic fibrosis. This drug is now in Phase II
human clinical testing.
Heale, J-P, Pollard A, Crookall K, Stokes, RW, Simpson D, Tsang A, Massing B, Speert, DP. Two distinct receptors
mediate nonosponic phagocytosis of different strains of Pseudomonas aeruginosa. J. Infect. Dis. 183: 1214-20, 2001.
Speert DP, Henry D, Vandamme P, Corey M, Mahenthiralingam E. Epidemiology of Burkholderia cepacia in Patients
with Cystic Fibrosis in Canada: Geographical Distribution and Clustering of Strains. Emerg. Infect. Dis. 8:181-187,
Chu KK, Davidson DJ, Halsey TK, Cheung JW, Speert DP. Differential persistence of the Burkholderia cepacia
complex in a murine model of pulmonary infection. Infect. Immun. 70:2715-2720, 2002.
Hirakata Y, Srikumar R, Poole K, Gotoh N, Suematsu T, Kohno S, Kamihira S, Hancock, REW, Speert DP. Multidrug
efflux plays an important role in the invasiveness of Pseudomonas aeruginosa J. Exp. Med. 196:109-118, 2002
Conway BD, Venu V, Speert DP. Biofilm formation and acyl-homoserine lactone production in the Burkholderia
cepacia complex. J. Bacteriol. 184: 5678-5685, 2002
Updated: August 2003
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