Dynamic Imaging of Experimental Leishmania donovani-Induced Hepatic Granulomas Detects Kupffer Cell-Restricted Antigen Presentation to Antigen-Specific CD8+ T Cells

Lynette Beattie, Adam Peltan, Asher Maroof, Alun Kirby, Najmeeyah Brown, Mark Coles, Deborah F. Smith, Paul M. Kaye

Research output: Contribution to journalArticlepeer-review

Abstract

Kupffer cells (KCs) represent the major phagocytic population within the liver and provide an intracellular niche for the survival of a number of important human pathogens. Although KCs have been extensively studied in vitro, little is known of their in vivo response to infection and their capacity to directly interact with antigen-specific CD8(+) T cells. Here, using a combination of approaches including whole mount and thin section confocal microscopy, adoptive cell transfer and intravital 2-photon microscopy, we demonstrate that KCs represent the only detectable population of mononuclear phagocytes within granulomas induced by Leishmania donovani infection that are capable of presenting parasite-derived peptide to effector CD8(+) T cells. This restriction of antigen presentation to KCs within the Leishmania granuloma has important implications for the identification of new candidate vaccine antigens and for the design of novel immuno-therapeutic interventions.

Original languageEnglish
Article numbere1000805
Number of pages17
JournalPLOS PATHOGENS
Volume6
Issue number3
DOIs
Publication statusPublished - 12 Mar 2010

Keywords

  • Animals
  • Antigen Presentation
  • Antigens, Protozoan
  • CD8-Positive T-Lymphocytes
  • Cell Movement
  • Granuloma
  • Kupffer Cells
  • Leishmania donovani
  • Leishmaniasis Vaccines
  • Leishmaniasis, Visceral
  • Liver
  • Macrophages
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phagocytosis

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