Equipe ATOMycA, U1232 CRCINA, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes, Université d'Angers, Angers, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-1163, Paris, France.
Sci Adv. 2020 Feb 26;6(9):eaax7781. doi: 10.1126/sciadv.aax7781. eCollection 2020 Feb.
Buruli ulcer, a neglected tropical infectious disease, is caused by . 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 . 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.
布鲁里溃疡是一种被忽视的热带传染病,由 引起。未经治疗,其病变可进展为慢性皮肤溃疡,但有 5%的病例会自发愈合,这表明宿主可能建立了一种对抗 的策略。我们在这里揭示了自发愈合过程中皮肤特异性局部体液特征,与抗体产生细胞的增加以及小鼠 IgG2a 免疫球蛋白亚类对 的特异性识别有关。我们证明了产生皮肤特异性抗体来中和 毒素的免疫调节活性,并通过在布鲁里溃疡患者中检测到抗 抗体,证实了人类宿主机制在触发有效的局部免疫反应方面的作用。我们的发现为根据世界卫生组织提出的最新挑战,在布鲁里溃疡的诊断和治疗方面取得重大进展铺平了道路。