<i>Salmonella</i> infection accelerates postnatal maturation of the intestinal epithelium
Abstract
Postnatal establishment of enteric metabolic, host–microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Salmonella Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators. Cytokine stimulation of neonatal intestinal epithelial stem cell organoids suggests a network of synergistic and antagonistic cytokine effects with a significant contribution of IL-22, IL-4/IL-13, TNF, and IL-6 to infection-induced enterocyte reprogramming. Our findings demonstrate that the infection-associated immune cell activation disrupts physiological postnatal tissue maturation and may thereby worsen clinical outcomes and alter the neonatal-adult transition.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (21)
Stefan Schlößer
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Anna-Lena Ullrich
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Nastaran Fazel Modares
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Matthias A. Schmitz
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Johannes Schöneich
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Kaiyi Zhang
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Isabel Richter
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Laura Robrahn
Institute for Computational Genomics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Sarah Schraven
Institute for Experimental Molecular Imaging, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
James S. Nagai
Institute for Computational Genomics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Sven-Bastiaan Haange
Department of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH—Helmholtz-Zentrum für Umweltforschung
Susan A. V. Jennings
Functional Microbiome Research Group, Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Thomas Clavel
Functional Microbiome Research Group, Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Ulrike Rolle-Kampczyk
Department of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH—Helmholtz-Zentrum für Umweltforschung
Fabian Kiessling
Institute for Experimental Molecular Imaging, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Ivan G. Costa
Institute for Computational Genomics, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Vanesa Muncan
Department of Gastroenterology and Hepatology, Tytgat Institute for Intestinal and Liver Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC University of Amsterdam
Urska Repnik
Central Microscopy Facility, University of Kiel
Martin von Bergen
Department of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH—Helmholtz-Zentrum für Umweltforschung
Aline Dupont
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Mathias W. Hornef
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital