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PMID: 15466622 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of experimental medicine ·Vol. 200 ·No. 7 ·2004-10-04 ·Pages 895-904

Amprey JL, Im JS, Turco SJ, Murray HW, Illarionov PA, Besra GS, Porcelli SA, Späth GF

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.

MeSH Terms
Animals Antigens, CD1/immunology,metabolism Antigens, CD1d Cell Separation DNA Primers Dendritic Cells/metabolism Female Flow Cytometry Glycosphingolipids/immunology,metabolism Interferon-gamma/immunology Killer Cells, Natural/immunology Leishmania donovani/chemistry Leishmaniasis, Visceral/immunology Liver/immunology Lymphocyte Activation Mice Mice, Mutant Strains RNA/genetics Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Antigens, CD1 Antigens, CD1d DNA Primers Glycosphingolipids lipophosphonoglycan RNA Interferon-gamma
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Amprey Joseph L
Department of Medicine, Weill College of Medicine, Cornell University, New York, NY 10021, USA.
Im Jin S
Turco Salvatore J
Murray Henry W
Illarionov Petr A
Besra Gurdyal S
Porcelli Steven A
Späth Gerald F
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20040704
Published
2004-10-04
Pages
895-904
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213292
Subset
IM
Grants
NIAID NIH HHS · R01 AI45889 · United States
NIGMS NIH HHS · GM07739 · United States
NIAID NIH HHS · R01 AI045889 · United States
NIAID NIH HHS · R01 AI048933 · United States
NIAID NIH HHS · AI 16963 · United States
NIAID NIH HHS · R56 AI016963 · United States
NIAID NIH HHS · P01 AI51392 · United States
NIGMS NIH HHS · T32 GM007739 · United States
NIAID NIH HHS · P01 AI051392 · United States
NIAID NIH HHS · R01 AI016963 · United States
NIAID NIH HHS · R01 AI48933 · United States
External Links
PubMed source DOI: 10.1084/jem.20040704 PMC Full Text View journal details
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