Staph aureus V8 protease drives itch via neuronal PAR1; gut TRPV1 neurons restrain Treg cells

A Global ImmunoTalks expert lecture described how Staphylococcus aureus secretes the V8 protease, encoded by sspA, which directly activates skin itch fibres by cleaving the neuronal PAR1 receptor, driving scratching and skin damage; sspA mutants and chromosomal complementation confirmed its necessity, and the FDA-approved PAR1 antagonist vorapaxar reduced itch and lesions. The talk also covered gut TRPV1 pain neurons releasing CGRP onto RAMP1 on Treg cells, suppressing colonic and ileal Treg proliferation and worsening DSS colitis and Citrobacter infection in mice, with bacterial spread to spleen and liver. Chemogenetic screening across eight neuronal subtypes showed TRPV1 neurons had the largest gut immune effect.