C. difficile intoxicates neurons and pericytes to drive neurogenic inflammation.

ABSTRACT: Clostridioides difficile infection (CDI) is a major cause of healthcare-associated gastrointestinal infections^1,2. The exaggerated colonic inflammation caused by C. difficile toxins such as toxin B (TcdB) damages tissues and promotes C. difficile colonization^3-6, but how TcdB causes inflammation is unclear. Here we report that TcdB induces neurogenic inflammation by targeting gut-innervating afferent neurons and pericytes through receptors, including the Frizzled receptors (FZD1, FZD2 and FZD7) in neurons and chondroitin sulfate proteoglycan 4 (CSPG4) in pericytes. TcdB stimulates the secretion of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) from neurons and pro-inflammatory cytokines from pericytes. Targeted delivery of the TcdB enzym

SUBMITTER: Manion J 

PROVIDER: S-EPMC11188852 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature