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 IFNγ 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.
Digital Object Identifier (DOI)
Amprey, Joseph L.; Im, Jin S.; Turco, Salvatore J.; Murray, Henry W.; Illarionov, Petr A.; Besra, Gurdyal S.; Porcelli, Steven A.; and Späth, Gerald F., "A Subset of Liver NK T Cells is Activated During Leishmania donovani Infection by CD1d-Bound Lipophosphoglycan" (2004). Molecular and Cellular Biochemistry Faculty Publication. 59.