Abstract Vomocytosis, also known as nonlytic exocytosis, is a process whereby fully phagocytosed microbes are expelled from phagocytes without discernible damage to either the phagocyte or microbe. Although this phenomenon was first described in the opportunistic fungal pathogen Cryptococcus neoformans in 2006, to date, mechanistic studies have been hampered by an inability to reliably stimulate or inhibit vomocytosis. Here we present the fortuitous discovery that macrophages lacking the scavenger receptor MAcrophage Receptor with COllagenous domain (MARCO), exhibit near-total vomocytosis of internalised cryptococci within a few hours of infection. Our findings suggest that MARCO’s role in modulating vomocytosis is independent of its role as a phagocytic receptor and instead may be driven by variation in cytoskeletal arrangement between wildtype and MARCO-deficient macrophages.

Loss of the scavenger receptor MARCO results in uncontrolled vomocytosis of fungi from macrophages