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

Lynette Beattie, Mattias Svensson, Alison Bune, Najmeeyah Brown, Asher Maroof, Soombul Zubairi, Katharine R. Smith, Paul M. Kaye

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)117-123
Number of pages7
JournalEuropean Journal of Immunology
Volume40
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • CD47
  • Invariant NKT cells
  • Kupffer cells
  • Signal regulatory protein alpha
  • INTEGRIN-ASSOCIATED PROTEIN
  • KILLER T-CELLS
  • DENDRITIC CELLS
  • GENE-EXPRESSION
  • DOWN-REGULATION
  • IMMUNE-SYSTEM
  • STEM-CELLS
  • SIRP-ALPHA
  • INFECTION

Cite this