Cited by 104Inflammatory Bowel DiseaseImmune Response and InflammationGut microbiota and health

Recurrent infection progressively disables host protection against intestinal inflammation

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Yang, Won Ho, Heithoff, Douglas M., Aziz, Peter V., Sperandio, Markus, Nizet, Victor, Mahan, Michael J., Marth, Jamey D.·2017·Science

Abstract

Minor infections cause big problems Pathogenic infection has been implicated in the chronic inflammation seen in inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease. Yang et al. show that recurrent, low-level, and fully resolving Salmonella enterica Typhimurium (ST) infections can precipitate severe colonic inflammation in mice. ST-induced TLR4 activation resulted in increased neuraminidase 3 (Neu3) production and activity in the duodenum. This led to intestinal alkaline phosphatase (IAP) desialylation and degradation. IAP deficiency caused a marked increase in commensal bacteria-generated lipopolysaccharide-phosphate in the colon, provoking inflammation. Treatment with calf IAP or the antiviral drug zanamivir (which inhibits Neu3 activity) prevented this inflammatory cascade. This pathway may serve as an effective target for future human IBD therapies. Science , this issue p. eaao5610

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  • Repeated Salmonella enterica infection in C57BL/6J mice caused intestinal inflammation and gradually impaired protective mechanisms by inducing endogenous neuraminidase, which lowered intestinal alkaline phosphatase levels and its protective effects.

    “In C57BL/6J mice, recurrent infection with Salmonella enterica promoted intestinal inflammation and progressively disabled protective mechanisms, inducing endogenous neuraminidase activity to reduce the abundance and protective effects of intestinal alkaline phosphatase.179”

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  1. [40]Schwerdtfeger SM Melzig MF Sialidases in biological systems Pharmazie 65 551 561 2010 20824954

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Authors
Yang, W. H., Heithoff, D. M., Aziz, P. V., Sperandio, M., Nizet, V., Mahan, M. J., & Marth, J. D.
Affiliations
  • University of California, Santa Barbara (US)
  • Institut für Chirurgische Forschung (DE)
  • University of California San Diego (US)
Corresponding author
Marth, Jamey D.
Venue
Science
Published
2017-12-22
Volume
358
Issue
6370
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2777913435
Cited by
104
References
72
Citations by year
2026: 11 · 2025: 12 · 2024: 13 · 2023: 12 · 2022: 11 · 2021: 15 · 2020: 10 · 2019: 8 · 2018: 11
FWCI
5.25
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (award358105, HL131474, award358106, HL125352, award358107, DK048247)
  • German Research Foundation (award343603, SFB914)
  • Wille Family Foundation (award343602)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
inflammatory bowel disease, ulcerative colitis, Crohn's disease, Salmonella typhimurium, recurrent infections, intestinal inflammation, TLR4, commensal bacteria, zanamivir, host defense
MeSH terms
beta-Galactoside alpha-2,3-Sialyltransferase, Alkaline Phosphatase, Animals, Colon, Enzyme Inhibitors, Lipopolysaccharides, Mice, Inbred C57BL, Neuraminidase, Recurrence, Salmonella Food Poisoning, Salmonella typhimurium, Sialyltransferases, Inflammatory Bowel Diseases, Toll-Like Receptor 4, Mice, Zanamivir

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