Interleukin-1β secretion induced by mucosal-associated gut commensal bacteria promotes intestinal barrier repair

• Published in: The Journal of immunology (1950) 2021-05, Vol.206 (1_Supplement), p.100-100.05
• Main Authors: Wu, Wan-Jung, Kim, Myunghoo, Morales, Fatima Beatriz Saldana, Ruiz, Daniel Fernando Zegarra, Hill, Andrea, Song, Hyo Won, Norwood, Kendra, Diehl, Gretchen
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.206.Supp.100.05

It is known that the gut commensal bacteria support intestinal epithelial barrier integrity. However, how specific microbes regulate barrier integrity is not fully understood. We and others find that barrier repair in models of colitis requires the microbiota and asked whether individual microbes are sufficient to replace functions of the total microbiota. We identified a mouse commensal E. coli that protects mice from enhanced damage in the absence of the microbiota in a mouse model of infectious colitis. Surprisingly, the protective E. coli induced IL-1β production by intestinal macrophages in vivo. Such IL-1β secretion activated type 3 innate lymphoid cells (ILC3) and induced IL-22 production that triggered epithelial barrier repair. In addition to mouse commensal E. coli, we also identified a subset of human E. coli isolates that offered protection utilizing the same cellular and molecular pathways. Together, we reveal a novel mechanism that select intestinal commensal bacteria activate inflammatory pathways to support gut barrier repair and maintain barrier integrity.