Title | A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan. |
Publication Type | Journal Article |
Year of Publication | 2004 |
Authors | Amprey JL, Im JS, Turco SJ, Murray HW, Illarionov PA, Besra GS, Porcelli SA, Späth GF |
Journal | J Exp Med |
Volume | 200 |
Issue | 7 |
Pagination | 895-904 |
Date Published | 2004 Oct 04 |
ISSN | 0022-1007 |
Keywords | Animals, Antigens, CD1, Antigens, CD1d, Cell Separation, Dendritic Cells, DNA Primers, Female, Flow Cytometry, Glycosphingolipids, Interferon-gamma, Killer Cells, Natural, Leishmania donovani, Leishmaniasis, Visceral, Liver, Lymphocyte Activation, Mice, Mice, Mutant Strains, Reverse Transcriptase Polymerase Chain Reaction, RNA |
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. |
DOI | 10.1084/jem.20040704 |
Alternate Journal | J. Exp. Med. |
PubMed ID | 15466622 |
PubMed Central ID | PMC2213292 |
Grant List | R01 AI45889 / AI / NIAID NIH HHS / United States GM07739 / GM / NIGMS NIH HHS / United States R01 AI045889 / AI / NIAID NIH HHS / United States R01 AI048933 / AI / NIAID NIH HHS / United States AI 16963 / AI / NIAID NIH HHS / United States R56 AI016963 / AI / NIAID NIH HHS / United States P01 AI51392 / AI / NIAID NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States P01 AI051392 / AI / NIAID NIH HHS / United States R01 AI016963 / AI / NIAID NIH HHS / United States R01 AI48933 / AI / NIAID NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:10pm