title: CD4 T Cell Dependent Colitis Exacerbation Following Re-Exposure ofMycobacterium aviumssp.paratuberculosis.
abstract: Mycobacterium aviumssp.paratuberculosis(MAP) is the causative agent of Johne's disease (JD), a chronic inflammatory bowel disease of cattle characterized by intermittent to chronic diarrhea. In addition, MAP has been isolated from Crohn's disease (CD) patients. The impact of MAP on severity of clinical symptoms in JD as well as its role in CD are yet unknown. We have previously shown that MAP is able to colonize inflamed enteric tissue and to exacerbate the inflammatory tissue response (Suwandi et al., 2014). In the present study, we analyzed how repeated MAP administration influences the course of dextran sulfate sodium (DSS)-induced colitis. In comparison to mice exposed to DSS or MAP only, repeated exposure of DSS-treated mice to MAP (DSS/MAP) revealed a significantly enhanced clinical score, reduction of colon length as well as severe CD4+T cell infiltration into the coloniclamina propria. Functional analysis identified a critical role of CD4+T cells in the MAP-induced disease exacerbation. Additionally, altered immune responses were observed when closely related mycobacteria species such asM. aviumssp.aviumandM. aviumssp.hominissuiswere administered. These data reveal the specific ability of MAP to aggravate intestinal inflammation and clinical symptoms. Overall, this phenotype is compatible with similar disease promoting capabilites of MAP in JD and CD.
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection ResearchBraunschweig, Germany; German Centre for Infection Research, Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical SchoolHannover, Germany.
authors.forename: Abdulhadi
authors.initials: A
authors.lastname: Suwandi
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research Braunschweig, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Bargen
authors.affiliation: Mouse Pathology, Helmholtz Centre for Infection Research Braunschweig, Germany.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Pils
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research Braunschweig, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Krey
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research Braunschweig, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Zur Lage
authors.affiliation: Department of Gastroenterology, Hepatology, Endocrinology, Hannover Medical School Hannover, Germany.
authors.forename: Anurag K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Institute for Microbiology, University of Veterinary Medicine Hannover Hannover, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Basler
authors.affiliation: Integrated Research and Treatment Center Transplantation, Institute of Transplant Immunology, Hannover Medical School Hannover, Germany.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
authors.affiliation: Department of Gastroenterology, Hepatology, Endocrinology, Hannover Medical School Hannover, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
authors.affiliation: Institute of Medical Microbiology, RWTH University Hospital Aachen Aachen, Germany.
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Hornef
authors.affiliation: Institute for Microbiology, University of Veterinary Medicine Hannover Hannover, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Goethe
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection ResearchBraunschweig, Germany; Institute of Immunology, Hannover Medical SchoolHannover, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003106:Colon / Q000473:pathology; D003424:Crohn Disease / Q000473:pathology; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D051379:Mice; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology* / Q000472:pathogenicity*; D010283:Paratuberculosis / Q000473:pathology*
chemical_list: D016264:Dextran Sulfate
keywords: CD4+T cells; DSS; MAP; colitis; repeated infection