A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan.
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| 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 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.
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| Authors | Joseph L Amprey, Jin S Im, Salvatore J Turco, Henry W Murray, Petr A Illarionov, Gurdyal S Besra, Steven A Porcelli, Gerald F Späth |
| Journal | The Journal of experimental medicine (J Exp Med) Vol. 200 Issue 7 Pg. 895-904 (Oct 04 2004) ISSN: 0022-1007 [Print] United States |
| PMID | 15466622 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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