ILC3s restrict the dissemination of intestinal bacteria to safeguard liver regeneration after surgery
Manuel O. Jakob,
Daniel Spari,
Daniel Sànchez Taltavull,
Lilian Salm,
Bahtiyar Yilmaz,
Rémi Doucet Ladevèze,
Catherine Mooser,
David Pereyra,
Ye Ouyang,
Theresa Schmidt,
Irene Mattiola,
Patrick Starlinger,
Deborah Stroka,
Franziska Tschan,
Daniel Candinas,
Georg Gasteiger,
Christoph S.N. Klose,
Andreas Diefenbach,
Mercedes Gomez de Agüero,
Guido Beldi
Affiliations
Manuel O. Jakob
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Institute of Microbiology, Infectious Diseases and Immunology (I-MIDI), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany; Corresponding author
Daniel Spari
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Daniel Sànchez Taltavull
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Lilian Salm
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Bahtiyar Yilmaz
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, 3008 Bern, Switzerland
Rémi Doucet Ladevèze
Institute of Systems Immunology, Max Planck Research Group, Julius-Maximilians-Universität Würzburg, Versbacherst 9, 97078 Würzburg, Germany
Catherine Mooser
Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, 3008 Bern, Switzerland
David Pereyra
Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, General Hospital of Vienna, Vienna, Austria
Ye Ouyang
Institute of Systems Immunology, Max Planck Research Group, Julius-Maximilians-Universität Würzburg, Versbacherst 9, 97078 Würzburg, Germany
Theresa Schmidt
Institute of Systems Immunology, Max Planck Research Group, Julius-Maximilians-Universität Würzburg, Versbacherst 9, 97078 Würzburg, Germany
Irene Mattiola
Institute of Microbiology, Infectious Diseases and Immunology (I-MIDI), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
Patrick Starlinger
Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, General Hospital of Vienna, Vienna, Austria
Deborah Stroka
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Franziska Tschan
Institute for Work and Organizational Psychology, University of Neuchâtel, Neuchâtel, Switzerland
Daniel Candinas
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Georg Gasteiger
Institute of Systems Immunology, Max Planck Research Group, Julius-Maximilians-Universität Würzburg, Versbacherst 9, 97078 Würzburg, Germany
Christoph S.N. Klose
Institute of Microbiology, Infectious Diseases and Immunology (I-MIDI), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
Andreas Diefenbach
Institute of Microbiology, Infectious Diseases and Immunology (I-MIDI), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
Mercedes Gomez de Agüero
Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, 3008 Bern, Switzerland; Institute of Systems Immunology, Max Planck Research Group, Julius-Maximilians-Universität Würzburg, Versbacherst 9, 97078 Würzburg, Germany
Guido Beldi
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Corresponding author
Summary: 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.
