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

Cell Reports (Mar 2023)

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

Journal volume & issue: Vol. 42, no. 3
p. 112269

Abstract

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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.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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