Abstract
<title>Abstract</title> <p>Clostridioides difficile infection is a leading cause of healthcare-associated diarrhea, characterized by massive neutrophil infiltration. Following antibiotic-induced dysbiosis, C. difficile colonizes the hypoxic colonic mucosa, where neutrophils contribute to tissue damage by exacerbating the inflammatory response. Here, we investigated the interaction between C. difficile and neutrophils under hypoxic conditions, mimicking the infected dysbiotic colon. C. difficile triggers neutrophil activation, myeloperoxidase degranulation, reactive oxygen species production, and the release of the recently characterized proteoglycofili. We showed that the CDT binary toxin, mainly the CDTb subunit, is responsible for these responses. In a conventional mouse model, CDT triggered pro-inflammatory cytokines expression and neutrophils recruitment. We further demonstrated that cdtAB expression is induced by low-oxygen tension through LuxS-dependent regulation. We assume that CDT probably exacerbated inflammatory response observed in severe C. difficile infections especially in pseudomembranous colitis.</p>