Tick peptides evoke itch by activating MrgprC11/MRGPRX1 to sensitize TRPV1 in pruriceptors

BackgroundTick bites severely threaten human health because they allow the transmission of many deadly pathogens, including viruses, bacteria, protozoa, and helminths. Pruritus is a leading symptom tick bites, but its molecular neural bases remain elusive.ObjectivesThis study sought to discover potent drugs targets for specific prevention treatment bite–induced pruritus arthropod-related itch.MethodsWe used live-cell calcium imaging, patch-clamp recordings, genetic ablation evaluated mouse behavior investigate pruritus.ResultsWe found that 2 salivary peptides, IP defensin 1 (IPDef1) IR (IRDef2), induced itch in mice. IPDef1 was further revealed have stronger pruritogenic potential than IRDef2 induce histamine-independent manner. evoked by activating MrgprC11 MRGPRX1 on dorsal root ganglion neurons. IPDef1-activated MrgprC11/X1 signaling sensitized downstream ion channel TRPV1 Moreover, also activated MrgprB2 ortholog MRGPRX2 selectively expressed mast cells, inducing release inflammatory cytokines driving acute inflammation mice, although cell activation did not contribute oxidated IPDef1–induced itch.ConclusionsOur identifies peptides as new class pruritogens initiate through MrgprC11/X1-TRPV1 pruritoceptors. Our work will provide drug or stings maybe other arthropods. Tick elusive. This itch. We pruritus.