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Infection and Immunity, December 2005, p. 8144-8152, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8144-8152.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Comparative Toll-Like Receptor 4-Mediated Innate Host Defense to Bordetella Infection

Paul B. Mann,1 Daniel Wolfe,1 Eicke Latz,2 Douglas Golenbock,2 Andrew Preston,3 and Eric T. Harvill1*

Pathobiology Graduate Program, Center for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park Pennsylvania,1 Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts,2 Department of Molecular and Cellular Biology, The University of Guelph, Guelph, Ontario, Canada3

Received 31 May 2005/ Returned for modification 1 July 2005/ Accepted 6 August 2005

Bordetella pertussis, B. parapertussis, and B. bronchiseptica are closely related species associated with respiratory disease in humans and other mammals. While B. bronchiseptica has a wide host range, B. pertussis and B. parapertussis evolved separately from a B. bronchiseptica-like progenitor to naturally infect only humans. Despite very different doubling times in vitro, all three establish similar levels of infection in the mouse lung within 72 h. Recent work has revealed separate roles for Toll-like receptor 4 (TLR4) in immunity to B. pertussis and B. bronchiseptica, while no role for TLR4 during B. parapertussis infection has been described. Here we compared the requirement for TLR4 in innate host defense to these organisms using the same mouse infection model. While B. bronchiseptica causes lethal disease in TLR4-deficient mice, B. pertussis and B. parapertussis do not. Correspondingly, TLR4 is critical in limiting B. bronchiseptica but not B. pertussis or B. parapertussis bacterial numbers during the first 72 h. Interestingly, B. bronchiseptica induces a TLR4-dependent cytokine response that is considerably larger than that induced by B. pertussis or B. parapertussis. Analysis of their endotoxins using RAW cells suggests that B. bronchiseptica lipopolysaccharide (LPS) is 10- and 100-fold more stimulatory than B. pertussis or B. parapertussis LPS, respectively. The difference in LPS stimulus is more pronounced when using HEK293 cells expressing human TLR4. Thus, it appears that in adapting to infect humans, B. pertussis and B. parapertussis independently modified their LPS to reduce TLR4-mediated responses, which may compensate for slower growth rates and facilitate host colonization.


* Corresponding author. Mailing address: Pathobiology Graduate Program, Immunology Research Laboratories, Department of Veterinary Science, The Pennsylvania State University, University Park, PA 16802. Phone: (814) 863-8522. Fax: (814) 863-6140. E-mail: eth10{at}psu.edu.

Editor: D. L. Burns


Infection and Immunity, December 2005, p. 8144-8152, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8144-8152.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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