Staph aureus V8 protease triggers itch through neuronal PAR1; gut TRPV1 neurons restrain Treg cells
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A Global ImmunoTalks expert lecture covered two findings linking the nervous and immune systems. 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 the protease's necessity, and the FDA-approved PAR1 antagonist vorapaxar reduced itch and lesions. Separately, gut TRPV1 pain neurons release CGRP onto RAMP1 on regulatory T cells, suppressing Treg proliferation in the colon and ileum 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 effect on gut immunity.
Written by a model from the reports · updated 2 hours ago
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- youtube.comStaph 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.
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