title: Local Cellular Immune Responses and Pathogenesis of Buruli Ulcer Lesions in the Experimental Mycobacterium Ulcerans Pig Infection Model.
abstract: BACKGROUND
  Buruli ulcer is a neglected tropical disease of the skin that is caused by infection with Mycobacterium ulcerans. We recently established an experimental pig (Sus scrofa) infection model for Buruli ulcer to investigate host-pathogen interactions, the efficacy of candidate vaccines and of new treatment options.
  
  
  RESULTS
  Here we have used the model to study pathogenesis and early host-pathogen interactions in the affected porcine skin upon infection with mycolactone-producing and non-producing M. ulcerans strains. Histopathological analyses of nodular lesions in the porcine skin revealed that six weeks after infection with wild-type M. ulcerans bacteria extracellular acid fast bacilli were surrounded by distinct layers of neutrophils, macrophages and lymphocytes. Upon ulceration, the necrotic tissue containing the major bacterial burden was sloughing off, leading to the loss of most of the mycobacteria. Compared to wild-type M. ulcerans bacteria, toxin-deficient mutants caused an increased granulomatous cellular infiltration without massive tissue necrosis, and only smaller clusters of acid fast bacilli.
  
  
  CONCLUSIONS
  In summary, the present study shows that the pathogenesis and early immune response to M. ulcerans infection in the pig is very well reflecting BU disease in humans, making the pig infection model an excellent tool for the profiling of new therapeutic and prophylactic interventions.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Bolz
authors.affiliation: Institute of Virology and Immunology (IVI), Mittelhäusern, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruggli
authors.affiliation: Institute of Veterinary Pathology, University of Zurich, Vetsuisse Faculty, Zurich, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Borel
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Ruf
mesh_terms: D000818:Animals; D054312:Buruli Ulcer / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D006651:Histocytochemistry; D054884:Host-Pathogen Interactions; D007111:Immunity, Cellular; D018942:Macrolides / Q000378:metabolism; D019911:Mycobacterium ulcerans / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000473:pathology; D013552:Swine; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D018942:Macrolides; D037521:Virulence Factors; C117218:mycolactone