Cellular Responses to Bacterial Cell Wall Components Are Mediated Through MyD88-dependent Signaling Cascades

Int Immunol. 2000 Jan;12(1):113-7. doi: 10.1093/intimm/12.1.113.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism*
  • Cell Wall / immunology*
  • Drosophila Proteins*
  • Gram-Negative Bacteria / immunology
  • Gram-Positive Bacteria / immunology
  • Lipopolysaccharides / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Mycobacterium / immunology
  • Myeloid Differentiation Factor 88
  • Peptidoglycan / immunology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic*
  • Signal Transduction
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Drosophila Proteins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Peptidoglycan
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Toll-Like Receptor 4
  • Toll-Like Receptors