Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE2

Yungi Kim, Kankanam Gamage Sanath Udayanga, Naoya Totsuka, Jason B. Weinberg, Gabriel Núñez, Akira Shibuya

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Summary Although imbalances in gut microbiota composition, or "dysbiosis," are associated with many diseases, the effects of gut dysbiosis on host systemic physiology are less well characterized. We report that gut dysbiosis induced by antibiotic (Abx) treatment promotes allergic airway inflammation by shifting macrophage polarization in the lung toward the alternatively activated M2 phenotype. Adoptive transfer of alveolar macrophages derived from Abx-treated mice was sufficient to increase allergic airway inflammation. Abx treatment resulted in the overgrowth of a commensal fungal Candida species in the gut and increased plasma concentrations of prostaglandin E2 (PGE2), which induced M2 macrophage polarization in the lung. Suppression of PGE2 synthesis by the cyclooxygenase inhibitors aspirin and celecoxib suppressed M2 macrophage polarization and decreased allergic airway inflammatory cell infiltration in Abx-treated mice. Thus, Abx treatment can cause overgrowth of particular fungal species in the gut and promote M2 macrophage activation at distant sites to influence systemic responses including allergic inflammation.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalCell Host and Microbe
Volume15
Issue number1
DOIs
Publication statusPublished - 2014 Jan 15
Externally publishedYes

Fingerprint

Dysbiosis
Dinoprostone
Fungi
Celecoxib
Macrophages
Inflammation
Lung
Cyclooxygenase Inhibitors
Macrophage Activation
Adoptive Transfer
Alveolar Macrophages
Candida
Aspirin
Therapeutics
Anti-Bacterial Agents
Phenotype

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE2. / Kim, Yungi; Udayanga, Kankanam Gamage Sanath; Totsuka, Naoya; Weinberg, Jason B.; Núñez, Gabriel; Shibuya, Akira.

In: Cell Host and Microbe, Vol. 15, No. 1, 15.01.2014, p. 95-102.

Research output: Contribution to journalArticle

Kim, Yungi ; Udayanga, Kankanam Gamage Sanath ; Totsuka, Naoya ; Weinberg, Jason B. ; Núñez, Gabriel ; Shibuya, Akira. / Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE2. In: Cell Host and Microbe. 2014 ; Vol. 15, No. 1. pp. 95-102.
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