A subset of Liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophospoglycan

Research output: Contribution to journalArticle

Authors

  • JL Amprey
  • JS Im
  • SJ Turco
  • HW Murray
  • SA Porcelli

Colleges, School and Institutes

Abstract

Natural killer (NK) T cells are activated by synthetic or self-glycolipids and implicated in innate host resistance to a range of viral, bacterial, and protozoan pathogens. Despite the immunogenicity of microbial lipoglycans and their promiscuous binding to CD1d, no pathogen-derived glycolipid antigen presented by this pathway has been identified to date. In the current work, we show increased susceptibility of NK T cell-deficient CD1d(-/-) mice to Leishmania donovani infection and Leishmania-induced CD1d-dependent activation of NK T cells in wild-type animals. The elicited response was Th1 polarized, occur-red as early as 2 h after infection, and was independent from IL-12. The Leishmania surface glycoconjugate lipophosphoglycan, as well as related glycoinositol phospholipids, bound with high affinity to CD1d and induced a CD1d-dependent IFNgamma response in naive intrahepatic lymphocytes. Together, these data identify Leishmania surface glycoconjugates as potential glycolipid antigens and suggest an important role for the CD1d-NK T cell immune axis in the early response to visceral Leishmania infection.

Details

Original languageEnglish
Pages (from-to)895-904
Number of pages10
JournalThe Journal of Experimental Medicine
Volume200
Early online date27 Sep 2004
Publication statusPublished - 27 Sep 2004

Keywords

  • CD1d antigen, glycoconjugates, Trypanosomatidae, natural immunity