Barrier tissues like the lung and gut serve as the primary interface between the host and the microbial world, requiring surveillance mechanisms to distinguish between commensal organisms and pathogens. Amongst the multitude of microbial detection mechanisms at barrier tissues, specialized epithelial sentinels called tuft cells monitor microbial signals using sensory mechanisms originally identified in lingual taste [1]. Tuft cells were first described in 1956 2, 3, but their functional significance remained enigmatic until three seminal studies revealed their crucial role in orchestrating type 2 immune responses against helminths and protists 4, 5, 6. These discoveries catalyzed intensive research into tuft cell biology, revealing numerous anti-helminth mechanisms and uncovering their previously unappreciated roles in responses to other microorganisms, including protists and viruses. Compared to their established role in helminth defense, the contribution of tuft cells to antiviral immunity is far less understood and appears context-dependent, varying by tissue, timing, and co-infection status.

This review synthesizes the current understanding of tuft cell function in anti-helminth and antiviral immunity. We first outline the well-characterized mechanisms by which tuft cells coordinate anti-helminth responses, establishing the foundational tuft cell–group 2 innate lymphoid cell (ILC2) circuit and its key effector molecules. We then explore the emerging picture of tuft cell function in antiviral immunity, where their impact varies by tissue, timing, and viral context. Next, we examine viral–helminth co-infections, where tuft cells may act as molecular switches that determine the balance between type 1 and type 2 immune responses. Finally, we speculate on their involvement in sequential infections, identify unresolved questions, and propose priorities for future investigation.