Department of Dermatology, Nanjing Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province 510080, China.
Department of Dermatology, Nanjing Jinling Hospital, Nanjing, Jiangsu Province 210002, China.
J Mycol Med. 2023 May;33(2):101359. doi: 10.1016/j.mycmed.2023.101359. Epub 2023 Jan 16.
The overuse of antifungal and immunosuppressant drugs and the higher frequency of organ transplantation has resulted in mycosis being increasingly intractable, and there is a great need for the development of new therapies. Melanin is an important virulence factor that can inhibit the inflammatory response in the host and facilitate fungal survival by several methods. However, a recent study showed that the Akt/mTOR/HIF1α axis in macrophages was activated after melanin-binding proteins recognised the DHN melanin of Aspergillus fumigatus, with a resulting metabolic shift towards glycolysis (i.e., metabolic reprogramming). As a result, antimicrobial compounds (e.g., inflammatory mediators and reactive oxygen species) were increased to fight the fungal invasion. Actually, DHN melanin from other fungi and DOPA melanin can induce inflammation and stimulate the production of melanin-binding antibodies. In addition, DOPA melanin contains conserved repeating units that are similar to those of DHN melanin. Therefore, we evaluated the associated evidence to propose an interesting and reasonable hypothesis that melanin promotes inflammation by metabolic reprogramming, which could provide a research direction for antifungal therapy. It suggests that regulating the metabolism of immune cells can guide the inflammatory response against fungi, despite the presence of immunosuppressant melanin. Since the biochemical molecules of glycolysis are clearly described, regulating glycolysis in macrophages may be easier than inventing new antifungal drugs. Further clarification of our hypothesis may strengthen the candidacy of melanin for future antifungal vaccines.
抗真菌和免疫抑制剂药物的过度使用以及器官移植的频率增加，导致真菌感染越来越难以治疗，因此非常需要开发新的治疗方法。黑色素是一种重要的毒力因子，它可以通过多种方式抑制宿主的炎症反应，促进真菌的存活。然而，最近的一项研究表明，黑色素结合蛋白识别烟曲霉 DHN 黑色素后，巨噬细胞中的 Akt/mTOR/HIF1α 轴被激活，导致糖酵解代谢转移（即代谢重编程）。因此，增加了抗菌化合物（如炎症介质和活性氧）以抵抗真菌入侵。实际上，其他真菌的 DHN 黑色素和 DOPA 黑色素可以诱导炎症并刺激黑色素结合抗体的产生。此外，DOPA 黑色素含有与 DHN 黑色素相似的保守重复单元。因此，我们评估了相关证据，提出了一个有趣且合理的假设，即黑色素通过代谢重编程促进炎症，这为抗真菌治疗提供了一个研究方向。这表明，尽管存在免疫抑制剂黑色素，但调节免疫细胞的代谢可以指导针对真菌的炎症反应。由于糖酵解的生化分子描述得很清楚，因此调节巨噬细胞中的糖酵解可能比发明新的抗真菌药物更容易。进一步阐明我们的假设可能会增强黑色素作为未来抗真菌疫苗候选物的资格。
