title: Leishmania donovani-induced expression of signal regulatory protein alpha on Kupffer cells enhances hepatic invariant NKT-cell activation.
abstract: Signal regulatory protein alpha (SIRPalpha) and its cognate ligand CD47 have been documented to have a broad range of cellular functions in development and immunity. Here, we investigated the role of SIRPalpha-CD47 signalling in invariant NKT (iNKT) cell responses. We found that CD47 was required for the optimal production of IFN-gamma from splenic iNKT cells following exposure to the alphaGalCer analogue PBS-57 and in vivo infection of mice with Leishmania donovani. Surprisingly, although SIRPalpha was undetectable in the liver of uninfected mice, the hepatic iNKT-cell response to infection was also impaired in CD47-/- mice. However, we found that SIRPalpha was rapidly induced on Kupffer cells following L. donovani infection, via a mechanism involving G-protein-coupled receptors. Thus, we describe a novel amplification pathway affecting cytokine production by hepatic iNKT cells, which may facilitate the breakdown of hepatic tolerance after infection.
authors.affiliation: Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, UK.
authors.forename: Lynette
authors.initials: L
authors.lastname: Beattie
authors.forename: Mattias
authors.initials: M
authors.lastname: Svensson
authors.forename: Alison
authors.initials: A
authors.lastname: Bune
authors.forename: Najmeeyah
authors.initials: N
authors.lastname: Brown
authors.forename: Asher
authors.initials: A
authors.lastname: Maroof
authors.forename: Soombul
authors.initials: S
authors.lastname: Zubairi
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Smith
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kaye
mesh_terms: D000818:Animals; D051928:CD47 Antigen / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance; D007728:Kupffer Cells / Q000276:immunology*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*
chemical_list: D051928:CD47 Antigen; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic