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Infection and Immunity, August 2004, p. 4561-4569, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4561-4569.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Toll-Like Receptor 2 Represses Nonpilus Adhesin-Induced Signaling in Acute Infections with the Pseudomonas aeruginosa pilA Mutant

Department of Internal Medicine, Section of Molecular Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina,¹ Centre de Recherche en Infectiologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Université Laval, Sainte-Foy, Quebec, Canada²

Received 18 November 2003/ Returned for modification 25 February 2004/ Accepted 9 April 2004

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.

Editor: V. J. DiRita

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