Neu3 neuraminidase induction triggers intestinal inflammation and colitis in a model of recurrent human food-poisoning

Yang, Won Ho; Westman, Julia S.; Heithoff, Douglas M.; Sperandio, Markus; Cho, Jin Won; Mahan, Michael J. und Marth, Jamey D. (2021): Neu3 neuraminidase induction triggers intestinal inflammation and colitis in a model of recurrent human food-poisoning. In: Proceedings of the National Academy of Sciences of the United States of America, Bd. 118, Nr. 29, e2100937118

Abstract

Intestinal inflammation is the underlying basis of colitis and the inflammatory bowel diseases. These syndromes originate from genetic and environmental factors that remain to be fully identified. Infections are possible disease triggers, including recurrent human food-poisoning by the common foodborne pathogen Salmonella enterica Typhimurium (ST), which in laboratory mice causes progressive intestinal inflammation leading to an enduring colitis. In this colitis model, disease onset has been linked to Toll-like receptor-4-dependent induction of intestinal neuraminidase activity, leading to the desialylation, reduced half-life, and acquired deficiency of anti-inflammatory intestinal alkaline phosphatase (IAP). Neuraminidase (Neu) inhibition protected against disease onset;however, the source and identity of the Neu enzyme(s) responsible remained unknown. Herein, we report that the mammalian Neu3 neuraminidase is responsible for intestinal IAP desialylation and deficiency. Absence of Neu3 thereby prevented the accumulation of lipopolysaccharide-phosphate and inflammatory cytokine expression in providing protection against the development of severe colitis.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0027-8424
• Sprache: Englisch