Molecular mechanisms of type 2 innate immune sensing

Type 2 immunity protects against helminths and venoms, yet its dysregulation drives allergic diseases. Initiation occurs at barrier tissues, where epithelial cells detect perturbations and release alarmins, activating type 2 innate lymphoid cells and conditioning dendritic cells for T helper 2 priming. However, the framework of type 2 innate immune sensing remains largely incomplete. Critical gaps include the core immunostimulatory components of many stimuli and their host detection pathways. Recent advances, including tuft cell chemosensation, membrane pore formation as a common trigger, and the role of protein crystals and proteases in allergic inflammation, highlight emerging molecular principles. Unlike bacterial, viral, and fungal recognition via conserved molecular patterns, type 2 immunity often involves the sensing of perturbations and stress signals.