Clostridioides difficile spores stimulate inflammatory cytokine responses and induce cytotoxicity in macrophages

Po Jung Chiu, Jagat Rathod, Yu Ping Hong, Pei Jane Tsai, Yuan Pin Hung, Wen Chien Ko, Jenn Wei Chen, Daniel Paredes-Sabja, I. Hsiu Huang

Research output: Contribution to journalArticlepeer-review

Abstract

Clostridioides difficile is a gram-positive, spore-forming anaerobic bacterium, and the leading cause of antibiotic-associated diarrhea worldwide. During C. difficile infection, spores germinate in the presence of bile acids into vegetative cells that subsequently colonize the large intestine and produce toxins. In this study, we demonstrated that C. difficile spores can universally adhere to, and be phagocytosed by, murine macrophages. Only spores from toxigenic strains were able to significantly stimulate the production of inflammatory cytokines by macrophages and subsequently induce significant cytotoxicity. Spores from the isogenic TcdA and TcdB double mutant induced significantly lower inflammatory cytokines and cytotoxicity in macrophages, and these activities were restored by pre-exposure of the spores to either toxins. These findings suggest that during sporulation, spores might be coated with C. difficile toxins from the environment, which could affect C. difficile pathogenesis in vivo.

Original languageEnglish
Article number102381
JournalAnaerobe
Volume70
DOIs
Publication statusPublished - 2021 Aug

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Infectious Diseases

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