Menacing Mold: Recent Advances in Aspergillus Pathogenesis and Host Defense

The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans inhale several hundred to several thousand Aspergillus conidia (i.e., vegetative spores) daily and typically clear these in an asymptomatic manner. In immunocompromised individuals, Aspergillus conidia can germinate into tissue-invasive hyphae, disseminate, and cause invasive aspergillosis. In this review, we first discuss novel concepts in host defense against Aspergillus infections and emphasize new insights in fungal recognition and signaling, innate immune activation, and fungal killing. Second, the review focuses on novel concepts of Aspergillus pathogenesis and highlights emerging knowledge regarding fungal strain heterogeneity, stress responses, and metabolic adaptations on infectious outcomes. Mechanistic insight into the host–pathogen interplay is thus critical to define novel druggable fungal targets and to exploit novel immune-based strategies to improve clinical outcomes associated with aspergillosis in vulnerable patient populations.