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Infect. Immun. doi:10.1128/IAI.00934-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Lack of in vitro and in vivo recognition of Francisella subspecies LPS by Toll-like receptors

Departments of Immunology, Medicine, Medicinal Chemistry, Microbiology, and Genome Sciences. University of Washington, Seattle, Washington. United States of America, Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå, Sweden, Department of NBC-Analysis, Swedish Defence Research Agency, Umeå, Sweden

^* To whom correspondence should be addressed. Email: rkernst{at}u.washington.edu.

	Abstract

Francisella tularensis is an intracellular Gram-negative bacterium that is highly infectious and potentially lethal. Several subspecies exist of varying pathogenicity. Infection by only a few organisms is sufficient to cause disease depending on the model system. Lipopolysaccharide (LPS) of Gram-negative bacteria is generally recognized by Toll-like receptor (TLR) 4/MD-2 and induces a strong pro-inflammatory response. Examination of human clinical F. tularensis isolates revealed that human virulent Type A and Type B strains produced lipid A of similar structure to the non-human model pathogen of mice, F. novicida (Fn). Fn LPS or lipid A is neither stimulatory nor an antagonist for human and murine cells through TLR4 or TLR2. It does not appear to interact with TLR4 or MD-2, as it is not an antagonist to other stimulatory LPS. Consistent with these observations, aerosolization of Fn LPS or whole bacteria induced no inflammatory response in mice. These results suggest that poor innate recognition of F. tularensis allows the bacterium to evade early recognition by the host innate immune system to promote its pathogenesis for mammals.

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