Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades

Abstract

MyD88 is an adaptor molecule essential for signaling via the Toll-like receptor (TLR)/IL-1 receptor family. TLR4 is a member of the TLR family and a point mutation in the Tlr4 gene causes hyporesponsiveness to lipopolysaccharide (LPS) in C3H/HeJ mice. We have previously shown that both TLR4- and MyD88-deficient mice are hyporesponsive to LPS. In this study we examined the responsiveness of these two knockout mice to various bacterial cell wall components. Cells from TLR4-deficient mice responded to several kinds of LPS, peptidoglycan and crude cell wall preparation from Gram-positive bacteria and mycobacterial lysates. In contrast, macrophages and splenocytes from MyD88-deficient mice did not respond to any of the bacterial components we tested. These results show that MyD88 is essential for the cellular response to bacterial cell wall components.

Gram-positive bacteria, innate immunity, lipopolysaccharide, macrophage, Toll-like receptor

IL-1R IL-1 receptor, LTA lipoteichoic acid, LPS lipopolysaccharide, PGN peptidoglycan, TLR Toll-like receptor, TNF tumor necrosis factor