Dual role of TLR2 and myeloid differentiation factor 88 in a mouse model of invasive group B streptococcal disease. Journal of immunology (Baltimore, Md. : 1950) [J Immunol] Journal article

Title	Dual role of TLR2 and myeloid differentiation factor 88 in a mouse model of invasive group B streptococcal disease.
Author(s)	Mancuso G, Midiri A, Beninati C, Biondo C, Galbo R, Akira S, Henneke P, Golenbock D, Teti G
Institution	Department of Pathology and Experimental Microbiology, University of Messina Medical School, Messina, Italy.
Source	J Immunol 2004 May 15; 172(10):6324-9.
MeSH	Adaptor Proteins, Signal Transducing Aging Animals Animals, Newborn Antigens, Differentiation Comparative Study Disease Models, Animal Dose-Response Relationship, Immunologic Genetic Predisposition to Disease Immunity, Natural Membrane Glycoproteins Mice Mice, Inbred C57BL Mice, Knockout Receptors, Cell Surface Receptors, Immunologic Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Sepsis Streptococcal Infections Streptococcus agalactiae Toll-Like Receptor 2 Toll-Like Receptors Tumor Necrosis Factor-alpha
Abstract	Toll-like receptors (TLRs) are involved in pathogen recognition by the innate immune system. Different TLRs and the adaptor molecule myeloid differentiation factor 88 (MyD88) were previously shown to mediate in vitro cell activation induced by group B streptococcus (GBS). The present study examined the potential in vivo roles of TLR2 and MyD88 during infection with GBS. When pups were infected locally with a low bacterial dose, none of the TLR2- or MyD88-deficient mice, but all of the wild-type ones, were able to prevent systemic spread of GBS from the initial focus. Bacterial burden was higher in MyD88- than in TLR2-deficient mice, indicating a more profound defect of host defense in the former animals. In contrast, a high bacterial dose induced high level bacteremia in both mutant and wild-type mice. Under these conditions, however, TLR2 or MyD88 deficiency significantly protected mice from lethality, concomitantly with decreased circulating levels of TNF-alpha and IL-6. Administration of anti-TNF-alpha Abs to wild-type mice could mimic the effects of TLR2 or MyD88 deficiency and was detrimental in the low dose model, but protective in the high dose model. In conclusion, these data highlight a dual role of TLR2 and MyD88 in the host defense against GBS sepsis and strongly suggest TNF-alpha as the molecular mediator of bacterial clearance and septic shock.
Language	eng
Pub Type(s)	Journal Article
PubMed ID	15128822

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