<i>Salmonella</i> infection accelerates postnatal maturation of the intestinal epithelium
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 <i>Salmonella</i> 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.
Authors
- Laura Robrahn (ORCID: https://orcid.org/0000-0001-8747-517X)
- Vanesa Muncan (ORCID: https://orcid.org/0000-0003-4062-6430)
- Urška Repnik (ORCID: https://orcid.org/0000-0003-0775-924X)
- Ulrike Elisabeth Rolle-Kampczyk (ORCID: https://orcid.org/0000-0002-7728-6284)
- Susan A. V. Jennings
- J. Schöneich
- Fabian M. Kiessling (ORCID: https://orcid.org/0000-0002-7341-0399)
- Stefan Schlößer (ORCID: https://orcid.org/0009-0008-6081-7721)
- Mathias Walter Hornef (ORCID: https://orcid.org/0000-0001-6096-9110)
- Sarah Schraven (ORCID: https://orcid.org/0000-0002-0676-8622)
- James S. Nagai (ORCID: https://orcid.org/0000-0002-7655-7206)
- Ivan G. Costa (ORCID: https://orcid.org/0000-0003-2890-8697)
- Sven‐Bastiaan Haange (ORCID: https://orcid.org/0000-0003-2952-1152)
- Matthias Schmitz (ORCID: https://orcid.org/0009-0008-4418-4012)
- Thomas Clavel (ORCID: https://orcid.org/0000-0002-7229-5595)
- Martin von Bergen� (ORCID: https://orcid.org/0000-0003-2732-2977)
- Isabel Richter
- Kaiyi Zhang (ORCID: https://orcid.org/0000-0002-0525-5817)
- Aline Dupont (ORCID: https://orcid.org/0000-0002-5290-2810)
- Anna-Lena Ullrich
- Nastaran Fazel Modares
Institutions
- Helmholtz Centre for Environmental Research (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Medizinische Hochschule Hannover (DE)
- Amsterdam University Medical Centers (NL)
- University of Amsterdam (NL)
- RWTH Aachen University (DE)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1073/pnas.2403344122
- Citations
- 3
- Primary Topic
- Infant Nutrition and Health
- Type
- article
- Field-Weighted Citation Impact
- 0.93
Funders
- Amsterdam University Medical Centers
- Deutsche Forschungsgemeinschaft
- Universiteit van Amsterdam
- Bundesministerium für Bildung und Forschung
- Helmholtz-Zentrum für Umweltforschung
- Medizinischen Hochschule Hannover
- RWTH Aachen University
- Medizinische Fakultät, RWTH Aachen University
- HORIZON EUROPE European Research Council