title: Gut dysbiosis and neuroimmune responses to brain infection with Theiler's murine encephalomyelitis virus.
abstract: Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+and CD8+T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice.
authors.affiliation: Grupo de Neuroinmunología, Departamento de Neurobiología Funcional y de Sistemas, Instituto Cajal, CSIC, Madrid, Spain.|Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Carrillo-Salinas
authors.affiliation: Grupo de Neuroinmunología, Departamento de Neurobiología Funcional y de Sistemas, Instituto Cajal, CSIC, Madrid, Spain.|Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: L
authors.initials: L
authors.lastname: Mestre
authors.affiliation: Grupo de Neuroinmunología, Departamento de Neurobiología Funcional y de Sistemas, Instituto Cajal, CSIC, Madrid, Spain.|Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: M
authors.initials: M
authors.lastname: Mecha
authors.affiliation: Grupo de Neuroinmunología, Departamento de Neurobiología Funcional y de Sistemas, Instituto Cajal, CSIC, Madrid, Spain.|Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: A
authors.initials: A
authors.lastname: Feliú
authors.affiliation: Servicio de Microbiología, Hospital Universitario Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, and Red Española de Investigación en Patología Infecciosa (REIPI), Sevilla, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Del Campo
authors.affiliation: Immunology Department, Hospital Universitario Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Villarrubia
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), Spain.|Servei de Neurología-Neuroimmunología, Centre d'Esclerosi Múltiple de Catalunya, Valld'Hebron Institut de Recerca, Hospital Universitari Valld'Hebron, 08035 Barcelona, Spain.|Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain.
authors.forename: C
authors.initials: C
authors.lastname: Espejo
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), Spain.|Servei de Neurología-Neuroimmunología, Centre d'Esclerosi Múltiple de Catalunya, Valld'Hebron Institut de Recerca, Hospital Universitari Valld'Hebron, 08035 Barcelona, Spain.|Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain.
authors.forename: X
authors.initials: X
authors.lastname: Montalbán
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), Spain.|Multiple Sclerosis Unit, Neurology Department, University of Alcalá, Madrid, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Álvarez-Cermeño
authors.affiliation: Red Española de Esclerosis Múltiple (REEM), Spain.|Immunology Department, Hospital Universitario Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Villar
authors.affiliation: Grupo de Neuroinmunología, Departamento de Neurobiología Funcional y de Sistemas, Instituto Cajal, CSIC, Madrid, Spain.|Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: C
authors.initials: C
authors.lastname: Guaza
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D064806:Dysbiosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D015213:Neuroimmunomodulation; D013116:Spinal Cord / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000821:virology; D017945:Theilovirus / Q000276:immunology / Q000472:pathogenicity