Abstract
Although tuft cells were discovered over 60 years ago, their functions have long been enigmatic, especially in human health. Nonetheless, tuft cells have recently emerged as key orchestrators of the host response to diverse microbial infections in the gut and airway. While tuft cells are epithelial in origin, they exhibit functions akin to immune cells and mediate important interkingdom interactions between the host and helminths, protists, viruses, and bacteria. With broad intra- and intertissue heterogeneity, tuft cells sense and respond to microbes with exquisite specificity. Tuft cells can recognize helminth and protist infection, driving a type 2 immune response to promote parasite expulsion. Tuft cells also serve as the primary physiologic target of persistent murine norovirus (MNV) and promote immune evasion. Recently, tuft cells were also shown to be infected by rotavirus. Other viral infections, such as influenza A virus, can induce tuft cell–dependent tissue repair. In the context of coinfection, tuft cells promote neurotropic flavivirus replication by dampening antiviral adaptive immune responses. Commensal and pathogenic bacteria can regulate tuft cell abundance and function and, in turn, tuft cells are implicated in modulating bacterial infiltration and mucosal barrier integrity. However, the contribution of tuft cells to microbial sensing in humans and their resulting effector responses are poorly characterized. Herein, we aim to provide a comprehensive overview of microbial activation of tuft cells with an emphasis on tuft cell heterogeneity and differences between mouse and human tuft cell biology as it pertains to human health and disease.
Highlights
This review aims to provide a comprehensive overview of microbial activation of tuft cells with an emphasis on tuft cell heterogeneity and differences between mouse and human tuft cell biology as they relate to human health and disease
In the thymus, in addition to their canonical markers, tuft cells uniquely express antigen presentation hallmarks such as L1cam and genes that encode for major histocompatibility complex II proteins (H2-Aa, H2-Ab, and CD74) that support their function in thymocyte development and immune tolerance [9,52]
With a heavy reliance on mouse models, our understanding of human tuft cell biology remains impeded by the rarity of tuft cells in human scRNA-seq analyses, limited genetic modeling tools, and the fact that many human samples are derived from diseased patients
Summary
Chemosensory epithelial cells named for their characteristic tufted apical microvilli that project into the lumen of hollow organs [1]. ACh, in contrast, may be secreted in a noncanonical mechanism, as tuft cells do not detectably express the machinery required for ACh to undergo synaptic release [48] Based on their known signaling pathways, tuft cells have been linked to a wide variety of bodily functions, such as the establishment of T cell tolerance, cross talk with the nervous system, epithelial repair and remodeling, cell division, and luminal sensing of microbes [9,24,56– 60]. Through use of the canonical signal transduction pathways delineated, tuft cells can sense the luminal environment In responding to these microbes at steady state and during insult, tuft cells boast diverse functions ranging from regulating immunity, driving epithelial repair, and maintaining homeostasis. This review aims to provide a comprehensive overview of microbial activation of tuft cells with an emphasis on tuft cell heterogeneity and differences between mouse and human tuft cell biology as they relate to human health and disease
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