title: Leishmania-induced inhibition of macrophage antigen presentation analyzed at the single-cell level.
abstract: A number of studies have previously examined the capacity of intracellular Leishmania parasites to modulate the capacity of macrophages to process and present Ags to MHC class II-restricted CD4(+) T cells. However, the bulk culture approaches used for assessing T cell activation make interpretation of some of these studies difficult. To gain a more precise understanding of the interaction between Leishmania-infected macrophages and effector T cells, we have analyzed various parameters of T cell activation in individual macrophage-T cell conjugates. Leishmania-infected macrophages efficiently stimulate Ag-independent as well as Ag-dependent, TCR-mediated capping of cortical F-actin in DO.11 T cells. However, infected macrophages are less efficient at promoting the sustained TCR signaling necessary for reorientation of the T cell microtubule organizing center and for IFN-gamma production. A reduced ability to activate these T cell responses was not due to altered levels of surface-expressed MHC class II-peptide complexes. This study represents the first direct single-cell analysis of the impact of intracellular infection on the interaction of macrophages with T cells and serves to emphasize the subtle influence Leishmania has on APC function.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Meier
authors.forename: Mattias
authors.initials: M
authors.lastname: Svensson
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kaye
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology*; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007893:Leishmania donovani / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D021962:Membrane Microdomains / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D022101:Microtubule-Organizing Center / Q000378:metabolism / Q000469:parasitology / Q000502:physiology; D010047:Ovalbumin / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology
chemical_list: D000199:Actins; D006183:H-2 Antigens; C108513:H-2A antigen; C111390:OVA 323-339; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D010047:Ovalbumin