Richness and diversity of mammalian fungal communities shape innate and adaptive immunity in health and disease

Human holobiomes are networks of mutualistic interactions between human cells and complex communities of bacteria and fungi that colonize the human body. The immune system must tolerate colonization with commensal bacteria and fungi but defend against invasion by either organism. Molecular ecological surveys of the human prokaryotic microbiota performed to date have revealed a remarkable degree of bacterial diversity and functionality. However, there is a dearth of information regarding the eukaryotic composition of the microbiota. In this review, we describe the ecology and the human niches of our fungal “fellow travelers” in both health and disease, discriminating between passengers, colonizers, and pathogens based on the interaction of these fungi with the human immune system. We conclude by highlighting the need to reconsider the etiology of many fungal and immune-related diseases in the context of the crosstalk between the human system and its resident microbial communities.