College of Life and Health Sciences, Northeastern University, Shenyang, People's Republic of China.
NHC Key Laboratory of AIDS Immunology, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, Shenyang, People's Republic of China.
Emerg Microbes Infect. 2023 Dec;12(2):2244087. doi: 10.1080/22221751.2023.2244087.
Systemic infection with , a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments and vaccination of cryptococcosis are available. Here, we describe Prm1, a novel regulator of virulence cells exhibit extreme sensitivity to various environmental stress conditions. Furthermore, cells show deficiencies in the biosynthesis of chitosan and mannoprotein, which in turn result in impairment of cell wall integrity. Treatment of mice with heat-killed cells was found to facilitate the host immunological defence against infection with wild-type . Further investigation demonstrated that cells strongly promote pulmonary production of interferon-γ, leading to activation of macrophage M1 differentiation and inhibition of M2 polarization. Therefore, our findings suggest that Prm1 may be a viable target for the development of anti-cryptococcosis medications and, cells lacking Prm1 represent a promising candidate for a vaccine.
全身性感染是一种在全球范围内发现的危险且具有传染性的病原体，常导致致命性隐球菌肺炎和脑膜脑炎，目前尚无有效的治疗方法和 cryptococcosis 疫苗。在这里，我们描述了 Prm1，一种新型毒力调节因子，缺失该因子的细胞对各种环境应激条件表现出极高的敏感性。此外，缺失 Prm1 的细胞在几丁质和甘露糖蛋白的生物合成中表现出缺陷，这反过来又导致细胞壁完整性受损。用热灭活的细胞治疗小鼠可促进宿主对野生型感染的免疫防御。进一步的研究表明，缺失 Prm1 的细胞强烈促进肺部产生干扰素-γ，导致巨噬细胞 M1 分化的激活和 M2 极化的抑制。因此，我们的研究结果表明，Prm1 可能是开发抗 cryptococcosis 药物的一个可行靶点，缺失 Prm1 的细胞代表了疫苗的有希望的候选物。
