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

Joseph L. Amprey, Jin S. Im, Salvatore J. Turco, Henry W. Murray, Petr A. Illarionov, Gurdyal S. Besra, Steven A. Porcelli, Gerald F. Späth

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165 Scopus citations

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, occurred 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 IFN-γ 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 (US)
Pages (from-to)895-904
Number of pages10
JournalJournal of Experimental Medicine
Volume200
Issue number7
DOIs
StatePublished - Oct 4 2004

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Keywords

  • CD1d antigen
  • Glycoconjugates
  • Natural immunity
  • Trypanosomalidae

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Amprey, J. L., Im, J. S., Turco, S. J., Murray, H. W., Illarionov, P. A., Besra, G. S., Porcelli, S. A., & Späth, G. F. (2004). A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan. Journal of Experimental Medicine, 200(7), 895-904. https://doi.org/10.1084/jem.20040704