ILC3s restrict the dissemination of intestinal bacteria to safeguard liver regeneration after surgery

• Published in: Cell reports (Cambridge) Vol. 42; no. 3; p. 112269
• Main Authors: Jakob, Manuel O., Spari, Daniel, Sànchez Taltavull, Daniel, Salm, Lilian, Yilmaz, Bahtiyar, Doucet Ladevèze, Rémi, Mooser, Catherine, Pereyra, David, Ouyang, Ye, Schmidt, Theresa, Mattiola, Irene, Starlinger, Patrick, Stroka, Deborah, Tschan, Franziska, Candinas, Daniel, Gasteiger, Georg, Klose, Christoph S.N., Diefenbach, Andreas, Gomez de Agüero, Mercedes, Beldi, Guido
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.03.2023; Cell Press; Elsevier
• Subjects: Animals; antibacterial defense; antimicrobial peptides; CP: Immunology; IL-22; ILC3s; Immunity, Innate; innate lymphoid cells; Interleukins - metabolism; Liver Regeneration; Lymphocytes - metabolism; Mice; sepsis; Skin - metabolism; surgical infection; CP: Immunology; antibacterial defense; ILC3s; surgical infection; innate lymphoid cells; IL-22; liver regeneration; antimicrobial peptides; sepsis
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112269

It is generally believed that environmental or cutaneous bacteria are the main origin of surgical infections. Therefore, measures to prevent postoperative infections focus on optimizing hygiene and improving asepsis and antisepsis. In a large cohort of patients with infections following major surgery, we identified that the causative bacteria are mainly of intestinal origin. Postoperative infections of intestinal origin were also found in mice undergoing partial hepatectomy. CCR6+ group 3 innate lymphoid cells (ILC3s) limited systemic bacterial spread. Such bulwark function against host invasion required the production of interleukin-22 (IL-22), which controlled the expression of antimicrobial peptides in hepatocytes, thereby limiting bacterial spread. Using genetic loss-of-function experiments and punctual depletion of ILCs, we demonstrate that the failure to restrict intestinal commensals by ILC3s results in impaired liver regeneration. Our data emphasize the importance of endogenous intestinal bacteria as a source for postoperative infection and indicate ILC3s as potential new targets. [Display omitted] •Translocating intestinal bacteria cause surgery-related infections•Systemic dissemination of intestinal bacteria is restricted by ILC3s via IL-22•ILC3s promote antimicrobial peptide production in hepatocytes•The ILC3-controlled spread of intestinal bacteria limits liver regeneration Jakob et al. report that surgical infections in humans have an intestinal microbial signature and, thus, an enteric origin. Modeling surgery in mice indicates that ILC3s control the systemic spread of intestinal microbes via IL-22 and induction of antimicrobial peptides in hepatocytes. Therefore, ILC3s may be targeted to limit surgery-associated infections.