Leishmania-infected human dendritic cells clear their intracellular parasites by a mechanism involving the cytolytic effector molecules granzyme B and granulysin

Abstract

Leishmania are intracellular parasites that cause various human diseases ranging from self-healing cutaneous to fatal visceral leishmaniasis. Host cells are phagocytes, primarily macrophages, where the parasites neutralize innate immune defenses, proliferate and finally rupture the cells. Despite that, Leishmania infection induces vigorous T cell responses, which require antigen processing and presentation, and stimulation by phagocytes, importantly dendritic cells. It was not clear how to align blockade of phagocyte functions with efficient immune stimulation. Here we show that, in contrast to macrophages, human dendritic cells survive the infection and destroy the parasites. This process involves granzyme B and granulysin, two cytolytic molecules essential for destruction of infected or otherwise aberrant cells by cytolytic T cells and natural killer cells. The report for the first time shows that these molecules not only act in target cell lysis by cytolytic effector cells but also in intracellular processing of infectious agents by dendritic cells.