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

PLoS Pathogens

Lynette Beattie¹  Najmeeyah Brown¹  Adam Peltan¹  Alun Kirby¹  Paul M. Kaye¹  Asher Maroof¹  Mark Coles¹  Deborah F. Smith¹ 

[1] Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom

关键词: Granulomas;    T cells;    Leishmania donovani;    Cytotoxic T cells;    Parasitic diseases;    Amastigotes;    Macrophages;    Inflammation;   

DOI  :  10.1371/journal.ppat.1000805

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 intra-vital 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.

【 授权许可】

CC BY