The cytotoxic synergy between Clostridioides difficile toxin B and proinflammatory cytokines: an unholy alliance favoring the onset of Clostridioides difficile infection and relapses

Clostridioides difficile infection (CDI) represents an important health problem world-wide, with significant morbidity and mortality. This infection has also high recurrence rates, whose pathophysiological grounds are still poorly understood. Based on our experiments in vitro with Clostridioides difficile toxin B and existing experimental and clinical evidence, we propose that primary CDI and relapses might be favored by a mechanism that involves the enhancement of the toxicity of toxin B by proinflamma-tory cytokines, tumor necrosis factor alpha, and interferon gamma on the enteric glial cells and their network in an environment characterized by a strong dysmicrobism