High levels of susceptibility and T helper 2 response in MyD88-deficient mice infected with Leishmania major are interleukin-4 dependent

Infect Immun. 2003 Dec;71(12):7215-8. doi: 10.1128/IAI.71.12.7215-7218.2003.

Abstract

Myeloid differentiation protein 88 (MyD88) is a general adaptor for the signaling cascade through receptors of the Toll/IL-1R family. When infected with Leishmania major parasites, MyD88-deficient mice displayed a dramatically enhanced parasite burden in their tissues similar to that found in susceptible BALB/c mice. In contrast, MyD88 knockout mice did not develop ulcerating lesions despite a lack of interleukin-12 (IL-12) production and a predominant T helper 2 cell response. Blockade of IL-4 produced early (day 1) after infection restored a protective T helper 1 response in MyD88 knockout mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antibodies, Protozoan / blood
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Disease Susceptibility
  • Female
  • Interleukin-4 / metabolism*
  • Leishmania major / immunology
  • Leishmania major / isolation & purification
  • Leishmania major / pathogenicity*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology
  • Leishmaniasis, Cutaneous / physiopathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88
  • Receptors, Immunologic / deficiency*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Th1 Cells / immunology
  • Th2 Cells / immunology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies, Protozoan
  • Antigens, Differentiation
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Immunologic
  • Interleukin-4