Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells
- PMID: 27019327
- PMCID: PMC4860105
- DOI: 10.1038/nm.4068
Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells
Abstract
Commensal gut bacteria impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the microbiota has an impact on the outcome of acute brain injury. Here we show that antibiotic-induced alterations in the intestinal flora reduce ischemic brain injury in mice, an effect transmissible by fecal transplants. Intestinal dysbiosis alters immune homeostasis in the small intestine, leading to an increase in regulatory T cells and a reduction in interleukin (IL)-17-positive γδ T cells through altered dendritic cell activity. Dysbiosis suppresses trafficking of effector T cells from the gut to the leptomeninges after stroke. Additionally, IL-10 and IL-17 are required for the neuroprotection afforded by intestinal dysbiosis. The findings reveal a previously unrecognized gut-brain axis and an impact of the intestinal flora and meningeal IL-17(+) γδ T cells on ischemic injury.
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Comment in
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Gut microbiota: Gut bacteria affect post-ischaemic inflammation in stroke by modulating intestinal T cells.Nat Rev Gastroenterol Hepatol. 2016 May;13(5):250. doi: 10.1038/nrgastro.2016.64. Epub 2016 Apr 6. Nat Rev Gastroenterol Hepatol. 2016. PMID: 27033125 No abstract available.
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References
-
- Henninger N, Kumar R, Fisher M. Acute ischemic stroke therapy. Expert Rev Cardiovasc Ther. 2010;8:1389–1398. - PubMed
-
- Macrez R, et al. Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol. 2011;10:471–480. - PubMed
-
- Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–118. - PubMed
-
- Prinz I, Silva-Santos B, Pennington DJ. Functional development of γδ T cells. Eur J Immunol. 2013;43:1988–1994. - PubMed
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