Phagocytic podosomes enable efficient uptake of Candida auris by primary human macrophages

Abstract

The yeast Candida auris is an emerging pathogen of steadily increasing importance. Understanding the molecular mechanisms of C. auris uptake and intracellular processing by immune cells such as macrophages is thus critical for counteracting the spreading of respective infections. Here, we show that phagocytosis of C. auris cells by primary human macrophages involves the formation of dot-like F-actin-rich structures at C. auris-containing phagosomes that we characterize as phagocytic podosomes. We analyse the composition, architecture, and dynamics of these structures, showing that they constitute a specific and highly dynamic adaptation of the phagocytic actin network of macrophages. We also show that disruption of phagocytic podosomes is associated with reduced internalization of C. auris cells and delayed maturation of respective phagosomes. Our data provide novel insights into the uptake mechanism and cytoskeletal rearrangements upon internalization of Candida by immune cells, while also challenging the dogma of a generally uniform and continuous actin network within phagocytic cups. At the same time, we identify C. auris as the first pathophysiologically relevant target whose internalization involves the formation of phagocytic podosomes.