Type-I interferons promote innate immune tolerance in macrophages exposed to Mycobacterium ulcerans vesicles

PLoS Pathog. 2023 Jul 10;19(7):e1011479. doi: 10.1371/journal.ppat.1011479. eCollection 2023 Jul.

Abstract

Buruli ulcer is a chronic infectious disease caused by Mycobacterium ulcerans. The pathogen persistence in host skin is associated with the development of ulcerative and necrotic lesions leading to permanent disabilities in most patients. However, few of diagnosed cases are thought to resolve through an unknown self-healing process. Using in vitro and in vivo mouse models and M. ulcerans purified vesicles and mycolactone, we showed that the development of an innate immune tolerance was only specific to macrophages from mice able to heal spontaneously. This tolerance mechanism depends on a type I interferon response and can be induced by interferon beta. A type I interferon signature was further detected during in vivo infection in mice as well as in skin samples from patients under antibiotics regiment. Our results indicate that type I interferon-related genes expressed in macrophages may promote tolerance and healing during infection with skin damaging pathogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Buruli Ulcer* / microbiology
  • Immune Tolerance
  • Interferon Type I*
  • Macrolides
  • Macrophages
  • Mice
  • Mycobacterium ulcerans*

Substances

  • Interferon Type I
  • Macrolides

Grants and funding

This work was supported by the Fondation pour la Recherche Médicale (Equipe FRM, grant no. R20104NN, grant recipient EM), Agence Nationale de la Recherche (Labex IGO Program ANR-11-LABX-0016ANR, grant recipient JJ, and JCJC MyEvs, grant recipient EM) and the Fondation Raoul Follereau (Grant recipient LM). QB received a salary from FRM, and Y.B and L.E. from Foundation Raoul Follereau. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.