MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria: no role for either in macrophage listericidal activity

J Immunol. 2002 Oct 1;169(7):3869-75. doi: 10.4049/jimmunol.169.7.3869.

Abstract

We have assessed the requirements for Toll-like receptor (TLR) signaling in vivo during early infection with Listeria monocytogenes. Mice deficient for TLR2, a receptor required for the recognition of Gram-positive peptidoglycan, showed equivalent Listeria resistance to wild-type mice. However, mice deficient for MyD88, an adaptor molecule used by all TLRs, showed profound susceptibility with 3-4 logs greater Listeria burden and severe spleen and liver pathology at day 3 postinfection. Listeria-infected MyD88-deficient mice also showed markedly diminished IFN-gamma, TNF-alpha, and NO responses, despite evidence of macrophage activation and up-regulation of MHC class II molecules. We demonstrate that although minor MyD88-independent responses to live Listeria do occur, these are insufficient for normal host defense. Lastly, we performed experiments in vitro in which macrophages deficient in TLR2 or MyD88 were directly infected with Listeria: Although TLR signaling was required for macrophage NO and cytokine production in response to Listeria, handling and direct killing of Listeria by activated macrophages occurred by TLR2- and MyD88-independent mechanisms.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / physiology*
  • Bone Marrow Cells / enzymology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / microbiology
  • Drosophila Proteins*
  • Genetic Predisposition to Disease
  • Immunity, Innate / genetics
  • Inflammation / genetics
  • Inflammation / microbiology
  • Inflammation / prevention & control
  • Interferon-gamma / pharmacology
  • Listeria monocytogenes / growth & development
  • Listeria monocytogenes / immunology
  • Listeriosis / genetics
  • Listeriosis / immunology*
  • Listeriosis / microbiology*
  • Macrophage Activation / genetics
  • Macrophage Activation / immunology
  • Macrophages / enzymology
  • Macrophages / immunology*
  • Macrophages / microbiology*
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88
  • Nitric Oxide Synthase / deficiency
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / physiology
  • Nitric Oxide Synthase Type II
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • Toll-Like Receptor 2
  • Toll-Like Receptors

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Drosophila Proteins
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse