How does Candida kill macrophages?

Author:

Nathalie Uwamahoro, Timothy Tucey, Jiyoti Verma-Gaur, Yue Qu, Hsin-Hui Shen, James Vince, Thomas Naderer, Ana Traven

Date: 18 December 2015

Abstract:

Morphogenetic transitions between yeast and filamentous cell types modulate immune interactions of Candida albicans. Innate immune phagocytes, such as macrophages, are an important component of antifungal host defenses. It has long been known that the intracellular macrophage environment triggers the morphogenetic transition from yeast to hyphal cells. In macrophages, hyphal forms are recognized by immune pathways, such as the caspase-1 inflammasome, to initiate an inflammatory response. However, paradoxically, hyphal forms also enable C. albicans to escape from the macrophage by causing host cell lysis. The model was that the hyphal filaments break macrophages by growing through their membranes. We have recently shown that contrary to this model, activation of caspase 1-dependent inflammatory responses by C. albicans is intimately mechanistically linked to the escape of this pathogen from the macrophage. The link comes from the realization that C. albicans hyphae trigger a lytic, caspase-1-dependent programmed cell death pathway in macrophages known as pyroptosis, with concomitant release of the pathogen. Pyroptosis is an important component of the cidal effects of C. albicans on macrophages, but it is not the only mechanism. We have devised a live-cell imaging assay to monitor Candida-macrophage interactions in detail over 24 h, and used it to show that inactivation of pyroptosis delays, but does no prevent C. albicans-dependent macrophage cell death. In current work, we are exploring how fungal adaptation mechanisms in the harsh macrophage environment mediate phagocyte death.

Abstract Number: 790

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