Leishmania donovani-induced expression of signal regulatory protein alpha on Kupffer cells enhances hepatic invariant NKT-cell activation
AuthorBeattie, L; Svensson, M; Bune, A; Brown, N; Maroof, A; Zubairi, S; Smith, KR; Kaye, PM
Source TitleEuropean Journal of Immunology
University of Melbourne Author/sBeattie, Lynette
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsBeattie, L., Svensson, M., Bune, A., Brown, N., Maroof, A., Zubairi, S., Smith, K. R. & Kaye, P. M. (2010). Leishmania donovani-induced expression of signal regulatory protein alpha on Kupffer cells enhances hepatic invariant NKT-cell activation. EUROPEAN JOURNAL OF IMMUNOLOGY, 40 (1), pp.117-123. https://doi.org/10.1002/eji.200939863.
Access StatusOpen Access
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.
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