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Cell Host Microbe. 2014 Jan 15;15(1):95-102. doi: 10.1016/j.chom.2013.12.010.

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

Author information

1
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
2
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
3
Department of Pediatrics and Communicable Diseases, Microbiology, and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
4
Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
5
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. Electronic address: ashibuya@md.tsukuba.ac.jp.

Abstract

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.

PMID:
24439901
PMCID:
PMC3957200
DOI:
10.1016/j.chom.2013.12.010
[Indexed for MEDLINE]
Free PMC Article

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