A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan.
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.
Department of Medicine, Weill College of Medicine, Cornell University, New York, NY 10021, USA.
Joseph L
JL
Amprey
Jin S
JS
Im
Salvatore J
SJ
Turco
Henry W
HW
Murray
Petr A
PA
Illarionov
Gurdyal S
GS
Besra
Steven A
SA
Porcelli
Gerald F
GF
Späth
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism*; D055610:Antigens, CD1d; D002469:Cell Separation; D017931:DNA Primers; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006028:Glycosphingolipids / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D007893:Leishmania donovani / Q000737:chemistry*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018949:Antigens, CD1; D055610:Antigens, CD1d; D017931:DNA Primers; D006028:Glycosphingolipids; C008290:lipophosphonoglycan; D012313:RNA; D007371:Interferon-gamma