Protective or pathogenic? Tuft cells shape divergent immune outcomes in helminth and viral infections

Abstract

Tuft cells are epithelial sentinels that monitor the luminal environment at barrier sites throughout the body. Their function as crucial initiators of type 2 immunity against helminths and protists in the intestine emerged nearly a decade ago. Since then, key tuft cell mechanisms and effectors involved in anti-helminth immunity have been described, but their responses to a wider array of microbes, like viruses, remain far less understood. Here, we review the roles of tuft cells during both helminth and viral infections at barrier tissues like the lung and the gut. While tuft cells protect against parasite infections, they exhibit a wider and sometimes contradictory influence on viral infections and pathology. We explore the emerging and context-dependent role of tuft cells in antiviral responses and examine how tuft cells act as molecular switches during helminth–viral co-infections to dramatically alter infection outcomes.