Critical coordination of innate immune defense against Toxoplasma gondii by dendritic cells responding via their Toll-like receptors

Baidong Hou, Alicia Benson, Lili Kuzmich, Anthony L. DeFranco, Felix Yarovinsky

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Toll-like receptors (TLRs) play an important role in host defense against a variety of microbial pathogens. We addressed the mechanism by which TLRs contribute to host defense against the lethal parasite Toxoplasmagondii by using mice with targeted inactivation of the TLR adaptor protein myeloid differentiation primary response gene 88 (MyD88) in different innate cell types. Lack of MyD88 in dendritic cells (DCs), but not in macrophages or neutrophils, resulted in high susceptibility to the T. gondii infection. In the mice deficient in MyD88 in DCs, the early IL-12 response by DCs was ablated, the IFN-γ response by natural killer cells was delayed, and the recruited inflammatory monocytes were incapable of killing the T. gondii parasites. The T-cell response, although attenuated in these mice, was sufficient to eradicate the parasite during the chronic stage, provided that defects in DC activation were compensated by IL-12 treatment early after infection. These results demonstrate a central role of DCs in orchestrating the innate immune response to an intracellular pathogen and establish that defects in pathogen recognition by DCs can predetermine sensitivity to infection.

Original languageEnglish (US)
Pages (from-to)278-283
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number1
DOIs
StatePublished - Jan 4 2011

Keywords

  • Host-pathogen interactions
  • Innate immunity
  • Natural killer cells

ASJC Scopus subject areas

  • General

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