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TLR4 Participates in the Inflammatory Response Induced by the AAF/II Fimbriae From Enteroaggregative Escherichia coli

Alejandra Alvestegui1, Mauricio Olivares-Morales1, Ernesto Muñoz1

  • 1Departamento de Pediatría, Facultad de Medicina, Centro de Estudios Moleculares, Hospital Dr. Luis Calvo Mackenna, Universidad de Chile, Santiago, Chile.

Frontiers in Cellular and Infection Microbiology
|May 28, 2019
PubMed

Insights

Toll-like receptor 4 (TLR4) plays a key role in the inflammatory response to enteroaggregative Escherichia coli (EAEC) infections. Blocking TLR4 significantly reduces inflammatory markers like IL-8, suggesting it

Area of Science:

  • Microbiology
  • Immunology
  • Gastroenterology

Background:

  • Enteroaggregative Escherichia coli (EAEC) causes persistent diarrhea, particularly in vulnerable populations.
  • Aggregative adherence fimbriae (AAF) are crucial for EAEC colonization and inducing inflammation.
  • The specific host receptors involved in EAEC-induced inflammation remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Toll-like receptor 4 (TLR4) in the inflammatory response to EAEC infections.
  • To elucidate the mechanism by which AAF/II fimbriae interact with host cells to trigger inflammation.

Main Methods:

  • Utilized TLR2/TLR4 antagonist (OxPAPC) and TLR4-specific antagonist (TAK-242) on HT-29 intestinal cells.
  • Assessed the secretion of inflammatory marker IL-8 in response to EAEC and AAF/II fimbrial extract.
  • Analyzed the secretion of 38 inflammation-related cytokines and chemokines mediated by TLR4 and AAF/II fimbriae.

Main Results:

  • Blocking TLR4 significantly reduced IL-8 secretion in HT-29 cells exposed to EAEC or AAF/II fimbriae.
  • TLR4 antagonism led to decreased secretion of IL-8, GRO, and IL-4.
  • AAF/II fimbriae were implicated in TLR4-mediated secretion of multiple inflammatory biomarkers.

Conclusions:

  • TLR4 is a critical receptor mediating intestinal cell responses to EAEC AAF/II fimbriae.
  • Targeting TLR4 may offer a therapeutic strategy for managing EAEC-induced inflammation and diarrhea.

Keywords:
Aggregative adherence fimbriaeenteroaggregative E. coliinflammationinterleukin-8toll-like receptors

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