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 language | English (US) |
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Pages (from-to) | 895-904 |
Number of pages | 10 |
Journal | Journal of Experimental Medicine |
Volume | 200 |
Issue number | 7 |
DOIs | |
State | Published - Oct 4 2004 |
Keywords
- CD1d antigen
- Glycoconjugates
- Natural immunity
- Trypanosomalidae
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology