Lack of In Vitro and In Vivo Recognition of Francisella tularensis Subspecies Lipopolysaccharide by Toll-Like Receptors

• Published in: Infection and Immunity Vol. 74; no. 12; pp. 6730 - 6738
• Main Authors: Hajjar, Adeline M, Harvey, Megan D, Shaffer, Scott A, Goodlett, David R, Sjöstedt, Anders, Edebro, Helen, Forsman, Mats, Byström, Mona, Pelletier, Mark, Wilson, Christopher B, Miller, Samuel I, Skerrett, Shawn J, Ernst, Robert K
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.12.2006
• Subjects: Animals; Bacteriology; Biological and medical sciences; Cells, Cultured; Francisella novicida; Francisella tularensis; Francisella tularensis - immunology; Francisella tularensis - pathogenicity; Fundamental and applied biological sciences. Psychology; Host Response and Inflammation; Humans; Lipid A - chemistry; Lipid A - immunology; Lipid A - pharmacology; Lipopolysaccharides - chemistry; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Mice; Microbiology; Miscellaneous; Monocytes - drug effects; Toll-Like Receptor 2 - agonists; Toll-Like Receptor 2 - physiology; Toll-Like Receptor 4 - agonists; Toll-Like Receptor 4 - physiology; Microbiology; Lipopolysaccharide; Bacteria; Toll like receptor; Immunity; Recognition; Francisella tularensis
• ISSN: 0019-9567; 1098-5522; 1098-5522
• DOI: 10.1128/IAI.00934-06

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.