title: FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer.
abstract: Buruli ulcer, a debilitating disease, is caused by Mycobacterium ulcerans. The incidence of this neglected tropical disease is steadily increasing. As a rule, without treatment, skin ulcers occur and a lengthy healing process may be observed associated with severe functional disabilities. Mouse models are already available to study establishment of lesions or evaluation of therapy but a lack of a suitable animal model, mimicking all clinical stages, in particular the healing process, remains an obstacle to understand the pathophysiology of M. ulcerans infection. M. ulcerans was s.c. inoculated in three consanguine mouse strains, that is, BALB/c and C57BL/6, classically used to study mycobacterial infection, and FVB/N. Strikingly, FVB/N mice, although as sensitive as all other mouse strains with respect to M. ulcerans infection, presented a spontaneous healing after the ulcerative phase despite stable bacterial load, and mycolactone toxin was not detected in the healed tissues. The spontaneous healing process was accompanied by an activation of the innate immune system. The adaptive response initiated by FVB/N mice was not involved in the healing process and did not confer protection against M. ulcerans. Our work highlights the importance of innate immune responses to control M. ulcerans infection. This in vivo model of M. ulcerans infection now paves the way for new avenues of research toward the elucidation of critical stages of this disease, such as the characterization of the regulation of mycolactone production, a better understanding of the pathophysiology of M. ulcerans infection, and the development of new therapeutic strategies.
authors.affiliation: Equipe Atip-Avenir, Centre Régional de Recherche en Cancérologie Nantes/Angers, INSERM U892, CNRS U6299, Centre Hospitalier Universitaire d'Angers and Université d'Angers, 49100 Angers, France; estelle.marion@inserm.fr.
authors.forename: Estelle
authors.initials: E
authors.lastname: Marion
authors.affiliation: Équipe "Immunité Innée, INSERM U892, CNRS U6299, Université d'Angers, Labex Immunotherapy Graft-Oncology, 49100 Angers, France;
authors.forename: Ulrich
authors.identifier: http://orcid.org/0000-0001-7961-0378
authors.initials: U
authors.lastname: Jarry
authors.affiliation: Equipe Atip-Avenir, Centre Régional de Recherche en Cancérologie Nantes/Angers, INSERM U892, CNRS U6299, Centre Hospitalier Universitaire d'Angers and Université d'Angers, 49100 Angers, France;
authors.forename: Camille
authors.initials: C
authors.lastname: Cano
authors.affiliation: Service de Pathologie Cellulaire et Tissulaire, Centre Hospitalier Universitaire d'Angers, 49100 Angers, France;
authors.forename: Caroline
authors.identifier: http://orcid.org/0000-0001-5785-5083
authors.initials: C
authors.lastname: Savary
authors.affiliation: Équipe "Immunité Innée, INSERM U892, CNRS U6299, Université d'Angers, Labex Immunotherapy Graft-Oncology, 49100 Angers, France; Laboratoire d'Immunologie et d'Allergologie, Centre Hospitalier Universitaire d'Angers, 49100 Angers, France; and.
authors.forename: Céline
authors.identifier: http://orcid.org/0000-0002-6987-3120
authors.initials: C
authors.lastname: Beauvillain
authors.affiliation: Equipe Atip-Avenir, Centre Régional de Recherche en Cancérologie Nantes/Angers, INSERM U892, CNRS U6299, Centre Hospitalier Universitaire d'Angers and Université d'Angers, 49100 Angers, France;
authors.forename: Marie
authors.initials: M
authors.lastname: Robbe-Saule
authors.affiliation: Équipe "Immunité Innée, INSERM U892, CNRS U6299, Université d'Angers, Labex Immunotherapy Graft-Oncology, 49100 Angers, France;
authors.forename: Laurence
authors.initials: L
authors.lastname: Preisser
authors.affiliation: Équipe "Glycoconjugés dans les Réponses Immunes," INSERM U892, CNRS U6299, Université de Nantes, 44300 Nantes, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Altare
authors.affiliation: Équipe "Immunité Innée, INSERM U892, CNRS U6299, Université d'Angers, Labex Immunotherapy Graft-Oncology, 49100 Angers, France; Laboratoire d'Immunologie et d'Allergologie, Centre Hospitalier Universitaire d'Angers, 49100 Angers, France; and.
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.affiliation: Équipe "Immunité Innée, INSERM U892, CNRS U6299, Université d'Angers, Labex Immunotherapy Graft-Oncology, 49100 Angers, France; Laboratoire d'Immunologie et d'Allergologie, Centre Hospitalier Universitaire d'Angers, 49100 Angers, France; and.
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
authors.affiliation: Equipe Atip-Avenir, Centre Régional de Recherche en Cancérologie Nantes/Angers, INSERM U892, CNRS U6299, Centre Hospitalier Universitaire d'Angers and Université d'Angers, 49100 Angers, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Marsollier
mesh_terms: D000818:Animals; D054312:Buruli Ulcer / Q000382:microbiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D018942:Macrolides / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D019911:Mycobacterium ulcerans / Q000276:immunology*; D012075:Remission, Spontaneous; D013045:Species Specificity
chemical_list: D018942:Macrolides; C117218:mycolactone