The MyD88 protein 88 pathway is differently involved in immune responses induced by distinct substrains of Leishmania major

Eur J Immunol. 2010 Jun;40(6):1697-707. doi: 10.1002/eji.200939821.


Host resistance to Leishmania major is highly dependent on the development of a Th1 immune response. The TLR adaptator myeloid differentiation protein 88 (MyD88) has been implicated in the Th1 immune response associated with the resistant phenotype observed in C57BL/6 mice after infection with L. major. To investigate whether the MyD88 pathway is differentially used by distinct substrains of parasites, MyD88(-/-) C57BL/6 mice were infected with two substrains of L. major, namely L. major LV39 and L. major IR75. MyD88(-/-) mice were susceptible to both substrains of L. major, although with different kinetics of infection. The mechanisms involved during the immune response associated with susceptibility of MyD88(-/-) mice to L. major is however, parasite substrain-dependent. Susceptibility of MyD88(-/-) mice infected with L. major IR75 is a consequence of Th2 immune-deviation, whereas susceptibility of MyD88(-/-) mice to infection with L. major LV39 resulted from an impaired Th1 response. Depletion of regulatory T cells (Treg) partially restored IFN-gamma secretion and the Th1 immune response in MyD88(-/-) mice infected with L. major LV39, demonstrating a role of Treg activity in the development of an impaired Th1 response in these mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / biosynthesis
  • Disease Susceptibility / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Leishmania major / immunology
  • Leishmaniasis, Cutaneous / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88 / immunology*
  • Signal Transduction / immunology*
  • T-Lymphocyte Subsets / immunology*


  • Cytokines
  • Myeloid Differentiation Factor 88