Univ Angers, Nantes Université, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Angers, France.
Nantes Université, INSERM, CRTI, Nantes, France.
PLoS Pathog. 2023 Jul 10;19(7):e1011479. doi: 10.1371/journal.ppat.1011479. eCollection 2023 Jul.
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.
布鲁里溃疡是由溃疡分枝杆菌引起的慢性传染病。病原体在宿主皮肤中的持续存在与溃疡性和坏死性病变的发展有关，导致大多数患者永久性残疾。然而，据认为，很少有确诊病例通过未知的自我愈合过程得到解决。通过体外和体内小鼠模型以及溃疡分枝杆菌纯化囊泡和(mycolactone)，我们表明，先天免疫耐受的发展仅对能够自发愈合的小鼠巨噬细胞具有特异性。这种耐受机制依赖于 I 型干扰素反应，并可被干扰素β诱导。在体内感染小鼠以及接受抗生素治疗的患者皮肤样本中，进一步检测到 I 型干扰素特征。我们的研究结果表明，在皮肤损伤病原体感染期间，巨噬细胞中表达的 I 型干扰素相关基因可能促进耐受和愈合。
