title: Interferon regulatory factor 7 contributes to the control of Leishmania donovani in the mouse liver.
abstract: Optimal hepatic resistance to Leishmania donovani in mice requires the coordinated effort of a variety of leukocyte populations that together induce activation of local macrophages to a leishmanicidal state. Although nitric oxide and reactive oxygen intermediates are potent leishmanicidal effector molecules operating in the acquired phase of immunity, there have long been suggestions that other mechanisms of leishmanicidal activity exist. We recently discovered that Irf-7 regulates a novel innate leishmanicidal response in resident splenic macrophages that line the marginal zone. Here, we tested whether this mechanism also operates in Kupffer cells, the resident macrophage population of the liver and the major target for hepatic infection by L. donovani. Comparing the Kupffer cell responses in situ in B6 and B6.Irf-7(-/-) mice, we found no evidence that Irf-7 affected amastigote uptake or early survival. However, we did find that Irf-7-deficient mice had impaired acquired resistance to hepatic L. donovani infection. This phenotype was attributable to a reduction in the capacity of hepatic CD4(+) T cells, NK cells, and NKT cells to produce gamma interferon (IFN-γ) and also to defective induction of NOS2 in infected Kupffer cells. Our data therefore add interferon regulatory factor 7 (IRF-7) to the growing list of interferon regulatory factors that have effects on downstream events in the acquired cellular immune response to nonviral pathogens.
authors.affiliation: Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, Wentworth Way, York YO10 5YW, United Kingdom.
authors.forename: Lynette
authors.initials: L
authors.lastname: Beattie
authors.forename: Rebecca
authors.initials: R
authors.lastname: Phillips
authors.forename: Najmeeyah
authors.initials: N
authors.lastname: Brown
authors.forename: Benjamin M J
authors.initials: BM
authors.lastname: Owens
authors.forename: Neal
authors.initials: N
authors.lastname: Chauhan
authors.forename: Jane E
authors.initials: JE
authors.lastname: Dalton
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kaye
mesh_terms: D000818:Animals; D002469:Cell Separation; D005434:Flow Cytometry; D050839:Interferon Regulatory Factor-7 / Q000276:immunology* / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology* / Q000378:metabolism; D007893:Leishmania donovani / Q000276:immunology* / Q000378:metabolism; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse