Hidden battles: dissecting host–fungal interactions and immune heterogeneity in infection outcomes

Fungal infections remain a major global human health problem, responsible for billions of infections and millions of deaths each year. Dissecting the immune mechanisms that protect us against these infections is an important step toward developing alternative therapies for patients at risk for fungal diseases, who are typically immunocompromised. Understanding antifungal immune responses is complicated by heterogeneity within host cell populations, as well as in-host adaptation strategies employed by fungi, which may also drive multiple distinct populations during infection. In this article, I discuss our recent discoveries and that of the medical mycology field, which has used creative and interdisciplinary approaches to better define the multiple layers of complexity that influence host-fungal interactions and infection outcomes. Finally, I describe examples where fundamental discovery has translated into new treatment approaches for patients and may represent revolutionary changes for our growing field.