title: Conventional housing conditions attenuate the development of experimental autoimmune encephalomyelitis.
abstract: BACKGROUND
  The etiology of multiple sclerosis (MS) has remained unclear, but a causative contribution of factors outside the central nervous system (CNS) is conceivable. It was recently suggested that gut bacteria trigger the activation of CNS-reactive T cells and the development of demyelinative disease.
  
  
  METHODS
  C57BL/6 (B6) mice were kept either under specific pathogen free or conventional housing conditions, immunized with the myelin basic protein (MBP)-proteolipid protein (PLP) fusion protein MP4 and the development of EAE was clinically monitored. The germinal center size of the Peyer's patches was determined by immunohistochemistry in addition to the level of total IgG secretion which was assessed by ELISPOT. ELISPOT assays were also used to measure MP4-specific T cell and B cell responses in the Peyer's patches and the spleen. Ear swelling assays were performed to determine the extent of delayed-type hypersensitivity reactions in specific pathogen free and conventionally housed mice.
  
  
  RESULTS
  In B6 mice that were actively immunized with MP4 and kept under conventional housing conditions clinical disease was significantly attenuated compared to specific pathogen free mice. Conventionally housed mice displayed increased levels of IgG secretion in the Peyer's patches, while the germinal center formation in the gut and the MP4-specific TH17 response in the spleen were diminished after immunization. Accordingly, these mice displayed an attenuated delayed type hypersensitivity (DTH) reaction in ear swelling assays.
  
  
  CONCLUSIONS
  The data corroborate the notion that housing conditions play a substantial role in the induction of murine EAE and suggest that the presence of gut bacteria might be associated with a decreased immune response to antigens of lower affinity. This concept could be of importance for MS and calls for caution when considering the therapeutic approach to treat patients with antibiotics.
authors.affiliation: Department of Anatomy I, University of Cologne, Cologne, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Arndt
authors.affiliation: Department of Anatomy I, University of Cologne, Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hoffacker
authors.affiliation: Department of Anatomy I, University of Cologne, Cologne, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Zellmer
authors.affiliation: Department of Anatomy I, University of Cologne, Cologne, Germany.
authors.forename: Oktay
authors.initials: O
authors.lastname: Goecer
authors.affiliation: Department of Anatomy I, University of Cologne, Cologne, Germany.
authors.forename: Mascha S
authors.initials: MS
authors.lastname: Recks
authors.affiliation: Department of Anatomy and Cell Biology, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuerten
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology*; D018858:Germinal Center / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D018991:Myelin Proteolipid Protein