Leishmania-induced inhibition of macrophage antigen presentation analyzed at the single-cell

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 acti-vation 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- 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. The Journal of Immunology, 2003, 171: 6706–6713. M acrophages have many roles in the immune system,including acting as APCs and as effector cells in an-timicrobial immunity. Nevertheless, many important pathogens of humans, including those that cause tuberculosis, leishmaniasis, toxoplasmosis, and Chagas ’ disease, all seek resi-dence in macrophages. Such a lifestyle necessitates the develop