Salmonella infection accelerates postnatal maturation of the intestinal epithelium

• 成果类型: Article
• 署名作者: Schloesser, Stefan; Ullrich, Anna-Lena; Modares, Nastaran Fazel; Schmitz, Matthias A.; Schoeneich, Johannes; Zhang, Kaiyi; Richter, Isabel; Robrahn, Laura; Schraven, Sarah; Nagai, James S.; Haange, Sven-Bastiaan; Jennings, Susan A. V.; Clavel, Thomas; Rolle-Kampczyk, Ulrike; Kiessling, Fabian; Costa, Ivan G.; Muncan, Vanesa; Repnik, Urska; von Bergen, Martin; Dupont, Aline; Hornef, Mathias W.
• 署名单位: RWTH Aachen University; RWTH Aachen University Hospital; Hannover Medical School; RWTH Aachen University; RWTH Aachen University Hospital; RWTH Aachen University; RWTH Aachen University Hospital; RWTH Aachen University; RWTH Aachen University Hospital; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); RWTH Aachen University; RWTH Aachen University Hospital; RWTH Aachen University; RWTH Aachen University Hospital; University of Kiel; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9695
• DOI: 10.1073/pnas.2403344122
• 发表日期: 2025-01-07
• 关键词: global enteric multicenter; middle-income countries; paneth cells; microbiota; differentiation; expression; diarrhea; infants; innate

摘要

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.