| Title: |
Skin-specific antibodies neutralizing mycolactone toxin during the spontaneous healing of Mycobacterium ulcerans infection |
| Authors: |
Foulon, Mélanie; Pouchin, Amélie; Manry, Jeremy; Khater, Fida; Robbe-Saule, Marie; Durand, Amandine; Esnault, Lucille; Delneste, Yves; Jeannin, Pascale; Saint André, Jean-Paul; Croué, Anne; Altare, Frédéric; Abel, Laurent; Alcaïs, Alexandre; Marion, Estelle |
| Contributors: |
ATOMycA (CRCINA-ÉQUIPE 6); Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA); Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); Imagine - Institut des maladies génétiques (IMAGINE - U1163); Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM); Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7); Centre Hospitalier Universitaire d'Angers (CHU Angers); Host-Pathogen Interactions in the Regulation of Immune Responses (CRCINA-ÉQUIPE 5); This work was supported by INSERM, Atip Avenir program, Fondation Raoul Follereau–France, Agence Nationale de la Recherche (ANR) BU_SPONT_HEAL project (InfectEra project), Angers University REPAIR project, Société Française de Dermatologie, and the Pays de la Loire region (ARMINA project). J.M., L.A., and A.A. acknowledge support from the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant no. ANR-10-LABX-62-IBEID) and the ANR under the “Investments for the Future” program (grant no. ANR-10-IAHU-01). A.A. acknowledges support from the Fondation pour la Recherche Médicale (grant no. DMI20091117308); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010); ANR-15-IFEC-0006,BU_SPONT_HEAL,Transcriptome Analysis of Animal Models of Spontaneous Healing of Buruli Ulcer(2015); ANR-16-CE12-0023,MYCOPARADOX,Dissection de l'architecture génétique des réactions paradoxales dans la Lèpre et l'Ulcère de Buruli(2016) |
| Source: |
ISSN: 2375-2548 ; Science Advances ; https://inserm.hal.science/inserm-02512893 ; Science Advances , 2020, 6 (9), pp.eaax7781. ⟨10.1126/sciadv.aax7781⟩. |
| Publisher Information: |
CCSD; American Association for the Advancement of Science (AAAS) |
| Publication Year: |
2020 |
| Subject Terms: |
[SDV.CAN]Life Sciences [q-bio]/Cancer |
| Description: |
International audience ; Buruli ulcer, a neglected tropical infectious disease, is caused by Mycobacterium ulcerans. Without treatment, its lesions can progress to chronic skin ulcers, but spontaneous healing is observed in 5% of cases, suggesting the possible establishment of a host strategy counteracting the effects of M. ulcerans. We reveal here a skin-specific local humoral signature of the spontaneous healing process, associated with a rise in antibody-producing cells and specific recognition of mycolactone by the mouse IgG2a immunoglobulin subclass. We demonstrate the production of skin-specific antibodies neutralizing the immunomodulatory activity of the mycolactone toxin, and confirm the role of human host machinery in triggering effective local immune responses by the detection of anti-mycolactone antibodies in patients with Buruli ulcer. Our findings pave the way for substantial advances in both the diagnosis and treatment of Buruli ulcer in accordance with the most recent challenges issued by the World Health Organization. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/32133396; PUBMED: 32133396; PUBMEDCENTRAL: PMC7043917 |
| DOI: |
10.1126/sciadv.aax7781 |
| Availability: |
https://inserm.hal.science/inserm-02512893; https://inserm.hal.science/inserm-02512893v1/document; https://inserm.hal.science/inserm-02512893v1/file/ArticleFoulon2020Eq6.pdf; https://doi.org/10.1126/sciadv.aax7781 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.96C5F2E2 |
| Database: |
BASE |