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

JL Amprey, JS Im, SJ Turco, HW Murray, Petr Illarionov, Gurdyal Besra, SA Porcelli

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176 Citations (Scopus)


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


  • CD1d antigen
  • glycoconjugates
  • Trypanosomatidae
  • natural immunity


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