Viral infection triggers interferon-induced expulsion of live Cryptococcus neoformans by macrophages

Infectious diseases are typically studied in isolation, but in real life people often encounter multiple infections simultaneously. Here we investigate how the innate immune response to the fatal fungus Cryptococcus neoformans is influenced by viral coinfection. Whilst virally-infected macrophages retain a normal capacity to engulf and kill Cryptococci, they demonstrate a dramatically enhanced propensity to expel them through vomocytosis. Activation of vomocytosis is driven by type-I interferons, generic ‘antiviral’ molecules, which signal back to the infected macrophage, triggering expulsion of the fungus. We propose that this hitherto unobserved phenomenon represents a ‘reprioritisation’ pathway for innate immune cells, by which they can alter the frequency with which they expel one pathogen depending on the level of threat from a secondary infection.