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

被引:128
作者
Hajjar, Adeline M.
Harvey, Megan D.
Shaffer, Scott A.
Goodlett, David R.
Sjostedt, Anders
Edebro, Helen
Forsman, Mats
Bystrom, Mona
Pelletier, Mark
Wilson, Christopher B.
Miller, Samuel I.
Skerrett, Shawn J.
Ernst, Robert K.
机构
[1] Univ Washington, Dept Med, Seattle, WA 98195 USA
[2] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
[3] Univ Washington, Dept Med, Seattle, WA 98195 USA
[4] Univ Washington, Dept Med Chem, Seattle, WA 98195 USA
[5] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA
[6] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
[7] Umea Univ, Dept Clin Microbiol Clin Bacteriol, Umea, Sweden
[8] Swedish Def Res Agcy, Dept NBC Anal, Umea, Sweden
关键词
D O I
10.1128/IAI.00934-06
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 4 (TLR4)/MD-2 and induces a strong proinflammatory 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 nonhuman model pathogen of mice, Francisella novicida. F. novicida 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 F. novicida 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.
引用
收藏
页码:6730 / 6738
页数:9
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