title: 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.
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Benakis
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Brea
authors.affiliation: Immunology Program and Infectious Disease Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.|Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, New York, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Caballero
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Faraco
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Moore
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Murphy
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Sita
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Racchumi
authors.affiliation: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Lilan
authors.initials: L
authors.lastname: Ling
authors.affiliation: Immunology Program and Infectious Disease Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.|Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, New York, USA.|Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Costantino
authors.initials: C
authors.lastname: Iadecola
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Josef
authors.initials: J
authors.lastname: Anrather
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001522:Behavior, Animal; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D003713:Dendritic Cells / Q000276:immunology*; D064806:Dysbiosis / Q000276:immunology* / Q000382:microbiology; D000069467:Fecal Microbiota Transplantation; D005434:Flow Cytometry; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D007962:Leukocytes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D020521:Stroke / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; C556062:IL10 protein, mouse; D020381:Interleukin-17; D012333:RNA, Messenger; D012336:RNA, Ribosomal, 16S; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016753:Interleukin-10