The yeast Candida auris is an emerging pathogen. Understanding the molecular mechanisms of its uptake and processing by immune cells is thus critical for counteracting the spread of respective infections. We show that the 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 analyze the composition, architecture, and dynamics of these structures, showing that they constitute a specific adaptation of the phagocytic actin network. The disruption of phagocytic podosomes is associated with reduced internalization of C. auris and delayed phagosomal maturation. Our data provide detailed insights into cytoskeletal rearrangements upon internalization of Candida by immune cells while also demonstrating that the actin network within phagocytic cups is not necessarily uniform and continuous. At the same time, we identify C. auris as a pathophysiologically relevant target whose internalization involves the formation of phagocytic podosomes.
Sopelniak et al. (Fri,) studied this question.