title: Experimental colitis is exacerbated by concomitant infection with Mycobacterium avium ssp. paratuberculosis.
abstract: BACKGROUND
  Crohn's disease (CD) is a chronic inflammatory disorder of the human gastrointestinal tract. Although genetic, immunological, environmental, and bacterial factors have been implicated, the pathogenesis is incompletely understood. The histopathological appearance of CD strikingly resembles Johne's disease, a ruminant inflammatory bowel disease, caused by Mycobacterium avium ssp. paratuberculosis (MAP), but a causative role of MAP in CD has not been established. In this work, we hypothesized that MAP might exacerbate an already existing intestinal disease.
  
  
  METHODS
  We combined dextran sulfate sodium (DSS)-induced colitis with MAP infection in mice and monitored the immune response and bacterial count in different organs.
  
  
  RESULTS
  An increased size of liver and spleen was observed in DSS-treated and MAP-infected animals (DSS + MAP) as compared with DSS-treated uninfected (DSS + PBS) mice. Similarly, DSS treatment increased the number and size of MAP-induced liver granulomas and enhanced the MAP counts in enteric tissue. MAP infection in turn delayed the mucosal healing of DSS-induced tissue damage. Finally, high numbers of MAP were found in mesenteric fat tissue causing large granuloma and necrotic regions.
  
  
  CONCLUSIONS
  Taken together, we present an in vivo model to study the role of MAP infection in CD. Our results confirm the hypothesis that MAP is able to exacerbate existing intestinal inflammation.
authors.affiliation: *Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany; †Mouse Pathology, Helmholtz Centre for Infection Research, Braunschweig, Germany; ‡Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany; §Central Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, Germany; ‖Institute of Transplant Immunology, Integrated Research and Treatment Center, Hannover, Germany; and ¶Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Abdulhadi
authors.initials: A
authors.lastname: Suwandi
authors.forename: Imke
authors.initials: I
authors.lastname: Bargen
authors.forename: Bishnudeo
authors.initials: B
authors.lastname: Roy
authors.forename: Marina C
authors.initials: MC
authors.lastname: Pils
authors.forename: Martina
authors.initials: M
authors.lastname: Krey
authors.forename: Susanne
authors.initials: S
authors.lastname: Zur Lage
authors.forename: Tina
authors.initials: T
authors.lastname: Basler
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Hornef
authors.forename: Ralph
authors.initials: R
authors.lastname: Goethe
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology; D016264:Dextran Sulfate / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D007422:Intestines / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000472:pathogenicity*; D010283:Paratuberculosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000382:microbiology
chemical_list: D012333:RNA, Messenger; D016264:Dextran Sulfate