Invariant NKT cells are essential for the regulation of hepatic CXCL10 gene expression during Leishmania donovani infection.
Gamma interferon (IFN-gamma)-regulated chemokines of the CXC family have been implicated as key regulators of a variety of T-cell-dependent inflammatory processes. However, the cellular source(s) of IFN-gamma that regulates their early expression has rarely been defined. Here, we have directly addressed this question in mice after Leishmania donovani infection. Comparison of CXCL10 mRNA accumulation in normal and IFN-gamma-deficient mice confirmed an absolute requirement for IFN-gamma for sustained (24 h) expression of CXCL10 mRNA accumulation in this model. In normal mice, IFN-gamma was produced by both CD3int NK1.1+ NKT cells and CD3- NK1.1+ NK cells, as detected by intracellular flow cytometry. Strikingly, B6.Jalpha281-/- mice lacking NKT cells that express the invariant Valpha14Jalpha18 T-cell-receptor alpha chain, although retaining a significant population of IFN-gamma-producing NK cells and NKT cells, were unable to sustain CXCL10 mRNA accumulation. These data indicate that invariant NKT cells are indispensable for the regulation of hepatic CXCL10 gene expression during L. donovani infection.
Svensson
Mattias
M
Immunology and Infection Unit, Department of Biology, University of York, Heslington, York YO10 5YW, United Kingdom.
Zubairi
Soombul
S
Maroof
Asher
A
Kazi
Fatima
F
Taniguchi
Masaru
M
Kaye
Paul M
PM
D000818:Animals; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000502:physiology*; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; D012333:RNA, Messenger; D007371:Interferon-gamma