Compartmentalization of intestinal bacteria by hepatic ILC3s prevents infections after surgery

Jakob, Manuel O.; Sánchez-Taltavull, Daniel; Yilmaz, Bahtiyar; Malinka, Thomas; Mooser, Catherine; Spari, Daniel; Salm, Lilian A.; Freiburghaus, Katrin; Pereyra, David; Hapfelmeier, Siegfried; Masoodi, Mojgan; Starlinger, Patrick; Stroka, Deborah; Tschan, Franziska; Candinas, Daniel; Gomez de Agüero, Mercedes; Beldi, Guido (19 September 2019). Compartmentalization of intestinal bacteria by hepatic ILC3s prevents infections after surgery (bioRxiv). Cold spring Harbor Laboratory 10.1101/773150

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Infections after surgical interventions are assumed to be caused by contamination. We show by analyzing multicentric data of 6561 patients that surgical infections as well as sepsis had a predominantly enteric microbial signature irrespective of the type of surgery, suggesting failure of intestinal bacterial compartmentalization. In mice, we reveal that hepatic surgery induced dysregulation of intestinal and hepatic type 3 innate lymphoid cells (ILC3s) and intestinal leakage resulting in enteric bacterial translocation via lymphatic vessels. In the absence of hepatic ILC3s, inflammasome activation and the induction of antimicrobial peptide encoding genes, bacteria colonized remote systemic organs and impaired surgical outcomes. Conversely, mammalian-microbial commensalism is required for the education of host immunity to ensure optimal hepatic healing responses. In fact, microbial-derived products were sufficient for the induction of proliferative transcriptional networks in the mouse liver, as illustrated by serum transfer experiments, mass spectrometry and RNA expression analysis, indicating that the balanced exposure of the host to commensals is essential for recovery. This study reveals the intestinal origin of microbes causing complications after surgical interventions and highlights host protective mechanisms of controlled commensalism that prevent infections.

Item Type:

Working Paper

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Jakob, Manuel; Sánchez Taltavull, Daniel; Yilmaz, Bahtiyar; Malinka, Thomas; Mooser, Catherine; Spari, Daniel; Salm, Lilian; Freiburghaus, Katrin; Hapfelmeier, Siegfried Hektor; Masoodi, Mojgan; Keogh-Stroka, Deborah M.; Candinas, Daniel; Gomez de Agüero Tamargo, Maria de la Mercedes and Beldi, Guido

Subjects:

600 Technology > 610 Medicine & health

Series:

bioRxiv

Publisher:

Cold spring Harbor Laboratory

Language:

English

Submitter:

Siegfried Hektor Hapfelmeier-Balmer

Date Deposited:

03 Jan 2020 10:59

Last Modified:

03 Jan 2020 10:59

Publisher DOI:

10.1101/773150

BORIS DOI:

10.7892/boris.137416

URI:

https://boris.unibe.ch/id/eprint/137416

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