MyD88-dependent induction of allergic Th2 responses to intranasal antigen

J Clin Invest. 2005 Feb;115(2):459-67. doi: 10.1172/JCI22462.

Abstract

MyD88 is a common Toll-like receptor (TLR) adaptor molecule found to be essential for induction of adaptive Th1 immunity. Conversely, innate control of adaptive Th2 immunity has been shown to occur in a MyD88-independent manner. In this study, we show that MyD88 is an essential innate component in the induction of TLR4-dependent Th2 responses to intranasal antigen; thus we demonstrate what we believe to be a novel role for MyD88 in pulmonary Th2 immunity. Induction of the MyD88-independent type I IFN response to LPS is defective in the pulmonary environment. Moreover, in the absence of MyD88, LPS-induced upregulation of costimulatory molecule expression on pulmonary DCs is defective, in contrast to what has been observed with bone marrow-derived DCs (BMDCs). Reconstitution of Th2 responses occurs upon adoptive pulmonary transfer of activated BMDCs to MyD88-deficient recipients. Furthermore, the dependence of Th2 responses on MyD88 is governed by the initial route of antigen exposure; this demonstrates what we believe are novel site-specific innate mechanisms for control of adaptive Th2 immunity.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Administration, Intranasal
  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Dendritic Cells / transplantation
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology*
  • Hypersensitivity / pathology
  • Hypersensitivity / therapy
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • Immunotherapy, Adoptive
  • Lipopolysaccharides / administration & dosage
  • Lung / immunology*
  • Lung / pathology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myeloid Differentiation Factor 88
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Th2 Cells / immunology*
  • Toll-Like Receptor 4

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Lipopolysaccharides
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • lipopolysaccharide, E coli O55-B5
  • Ovalbumin