IL-27 induces LL-37/CRAMP expression from intestinal epithelial cells: implications for immunotherapy of Clostridioides difficile infection

Autor: Banglao Xu, Xianan Wu, Yi Gong, Ju Cao
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Gut Microbes, Vol 13, Iss 1 (2021)
Druh dokumentu: article
ISSN: 1949-0976
1949-0984
19490976
DOI: 10.1080/19490976.2021.1968258
Popis: Clostridioides difficile infection is currently the leading cause of nosocomial antibiotic-associated diarrhea and pseudomembranous colitis worldwide. Cathelicidins, a major group of natural antimicrobial peptides, have antimicrobial and immunomodulatory activities in Clostridioides difficile infection. Here, we have shown that cytokine IL-27 induced human cathelicidin antimicrobial peptide (LL-37) expression in primary human colonic epithelial cells. IL-27 receptor-deficient mice had impaired expression of cathelicidin-related antimicrobial peptide (CRAMP, mouse homolog for human LL-37) after Clostridioides difficile infection, and restoration of CRAMP improved Clostridium difficile clearance and reduced mortality in IL-27 receptor-deficient mice after Clostridioides difficile challenge. In clinical samples from 119 patients with Clostridioides difficile infection, elevated levels of IL-27 were positively correlated with LL-37 in the sera and stools. These findings suggest that IL-27 may be involved in host immunity against Clostridioides difficile infection via induction of LL-37/CRAMP. Therefore, IL-27-LL-37 axis may be a valuable pathway in the development of immune-based therapy.
Databáze: Directory of Open Access Journals