Toll-like receptor 2 represses nonpilus adhesin-induced signaling in acute infections with the Pseudomonas aeruginosa pilA mutant.
Expression of pili and associated proteins is an important means of host invasion by bacterial pathogens. Recent evidence has suggested that the binding of Pseudomonas aeruginosa through nonpilus adhesins may also be important in respiratory diseases, since adhesins bind mucins. Using wild-type C57BL/6 and TLR2KO mice, we compared the induction levels of the host response to P. aeruginosa that either expressed pili or lacked pilus expression due to a mutation in the structural gene pilA. In C57BL/6 mice, deletion of pili led to a decreased immune response, evidenced by a lower secretion of cytokines and a lack of neutrophil chemotaxis. By contrast, the P. aeruginosa pilA mutant induced a hyperresponsive phenotype in TLR2KO mice. TLR2KO mice showed an increased number of neutrophils in lavage fluid compared to the levels seen when either mouse strain was exposed to wild-type P. aeruginosa. Further analysis indicated that the increased neutrophil influx was associated with an increased expression of calgranulins, possibly through an induction of Toll-like receptor 4 (TLR4) expression. The hyperresponsive phenotype of TLR2KO mice exposed to the P. aeruginosa pilA mutant was associated with TLR4 induction and indicated that nonpilus adhesin-induced signaling was repressed by TLR2 function and, if not blocked by the host, could induce airway hyperresponsiveness.
Department of Internal Medicine, Section of Molecular Medicine, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157-1042, USA. elorenz@wfubmc.edu
Eva
E
Lorenz
Diana C
DC
Chemotti
Karen
K
Vandal
Philippe A
PA
Tessier
D000208:Acute Disease; D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D036781:Fimbriae Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007113:Immunity, Innate; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009504:Neutrophils / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D018829:Adhesins, Bacterial; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D036781:Fimbriae Proteins