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

Won Ho Yang, Julia S. Westman, Douglas M. Heithoff, Markus Sperandio, Jin Won Cho, Michael J. Mahan, Jamey D. Marth

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8 Citations (Scopus)


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.

Original languageEnglish
Article numbere2100937118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number29
Publication statusPublished - 2021 Jul 20

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. This research was funded by NIH Grants HL131474 (J.D.M. and M.J.M.) and DK048247 (J.D.M.), the Mizutani Foundation for Glycoscience (J.D.M.), and the Wille Family Foundation (J.D.M.). Additional support was provided by the Yonsei Research Fund (2019-22-0020) and the National Research Foundation of Korea (NRF) Ministry of Science, Information and Communications Technology (ICT), and Future Planning NRF-2016R1A5A1010764 and NRF-2020R1A2C101232911 (W.H.Y. and J.W.C).

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© 2021 National Academy of Sciences. All rights reserved.

All Science Journal Classification (ASJC) codes

  • General


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