Leishmania donovani-induced expression of signal regulatory protein α on Kupffer cells enhances hepatic invariant NKT-cell activation

Signal regulatory protein alpha (SIRP alpha) 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 SIRP alpha-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 alpha GalCer analogue PBS-57 and in vivo infection of mice with Leishmania donovani. Surprisingly, although SIRP alpha 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 SIRP alpha 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.