Candida albicans morphogenesis and host defence: discriminating invasion from colonization

Key Points Candida albicans is the most common fungal pathogen of humans, and also colonizes the skin and mucosal surfaces of most healthy individuals. Little was known about the mechanisms by which the mucosal immune response tolerates colonizing C. albicans yeast cells but reacts strongly when hyphae invade tissue. C. albicans yeast cells and hyphae differ in their morphological properties, and this has important consequences for their recognition by mucosal immune cells. Different mechanisms, in epithelial cells on the one hand and in immune cells on the other, are important for recognizing fungal invasion of the mucosa. The germination of hyphae and increased fungal loads are recognized by epithelial cells, which then release pro-inflammatory cytokines and chemokines though specific kinase-dependent pathways. Tissue macrophages recognize C. albicans hyphae through inflammasome activation mediated by a dectin 1-dependent pathway. In turn, this results in processing of pro-interleukin-1β and induction of T helper 17-type responses. These mechanisms provide a conceptual framework for our understanding of tolerance to colonization versus immune defence against invasion by C. albicans and probably also by other microorganisms. Candida albicans can grow as unicellular budding yeast cells and as filamentous hyphae. Mihai Netea and colleagues discuss the molecular mechanisms that drive this dimorphism, the changes that lead to differential interaction with the host, and the immunological mechanisms that discriminate between tissue colonization and invasion. Candida albicans is a common fungal pathogen of humans that colonizes the skin and mucosal surfaces of most healthy individuals. Until recently, little was known about the mechanisms by which mucosal antifungal defences tolerate colonizing C. albicans but react strongly when hyphae of the same microorganism attempt to invade tissue. In this Review, we describe the properties of yeast cells and hyphae that are relevant to their interaction with the host, and the immunological mechanisms that differentially recognize colonizing versus invading C. albicans .