Department of Immunology, National Vaccine Innovation Platform, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
NHC Key Laboratory of Antibody Technique, Jiangsu Key Laboratory of Pathogen Biology, Department of Immunology, Nanjing Medical University, Nanjing, China.
mBio. 2024 Oct 16;15(10):e0213024. doi: 10.1128/mbio.02130-24. Epub 2024 Sep 17.
Pulmonary cryptococcosis is a common complication in immunocompromised patients. In a mouse model of pulmonary cryptococcosis, induces a type 2 immune response that is detrimental to host protection. Long non-coding RNAs (lncRNAs) have emerged as key players in the pathogenesis of infectious diseases. However, the roles and mechanisms of lncRNAs in fungal infection are largely elusive. In the present study, we aimed to explore the roles of LincR-PPP2R5C in pulmonary cryptococcosis. We observed an increase in the level of LincR-PPP2R5C in the lung tissues of C57BL/6J mice after tracheal infection with . Subsequently, we intratracheally infected LincR-PPP2R5C knockout (KO) mice and wild-type mice with . LincR-PPP2R5C deficiency mitigates infection, which can be demonstrated by extending survival time and decreasing fungal burden in the lung. In the lung tissues of infected LincR-PPP2R5C KO mice, there was a notable increase in the levels of type 2 cytokines [interleukin (IL)-4 and IL-5] and an increase in the number of neutrophils in both the lung tissue and bronchoalveolar lavage fluid. Mechanistically, the lack of LincR-PPP2R5C results in increased protein phosphatase 2A phosphorylation, thereby enhancing the fungicidal activity of neutrophils against , with IL-4 playing a synergistic role in this process. Overall, LincR-PPP2R5C deficiency mitigated pulmonary cryptococcosis by increasing the fungicidal activity of neutrophils, which was associated with increased IL-4 levels. Our study presented specific evidence of the role of host-derived lncRNAs in the regulation of infection.
Pulmonary cryptococcosis is a human fungal disease caused by , which is common not only in immunocompromised individuals but also in patients with normal immune function. Therefore, studying the control mechanisms of pulmonary cryptococcosis is highly important. Here, we demonstrated that the deletion of LincR-PPP2R5C leads to increased killing of by neutrophils, thereby reducing pulmonary cryptococcal infection. These findings will greatly enhance our understanding of the mechanisms by which lncRNAs regulate the pathogenesis of , facilitating the use of lncRNAs in pulmonary cryptococcosis therapy.
肺隐球菌病是免疫功能低下患者的常见并发症。在肺隐球菌病的小鼠模型中， 诱导 2 型免疫反应，对宿主保护不利。长链非编码 RNA（lncRNA）已成为传染病发病机制的关键因素。然而，lncRNA 在真菌感染中的作用和机制在很大程度上仍不清楚。在本研究中，我们旨在探讨 LincR-PPP2R5C 在肺隐球菌病中的作用。我们观察到， 在感染 C57BL/6J 小鼠的气管后，肺组织中的 LincR-PPP2R5C 水平升高。随后，我们通过气管内感染 LincR-PPP2R5C 敲除（KO）小鼠和野生型小鼠来感染 。LincR-PPP2R5C 缺失减轻了 感染，这可以通过延长感染小鼠的生存时间和减少肺部真菌负荷来证明。在感染 LincR-PPP2R5C KO 小鼠的肺组织中，2 型细胞因子（白细胞介素 [IL]-4 和 IL-5）水平显著升高，肺组织和支气管肺泡灌洗液中的中性粒细胞数量也增加。在机制上，缺乏 LincR-PPP2R5C 导致蛋白磷酸酶 2A 磷酸化增加，从而增强中性粒细胞对 的杀菌活性，而 IL-4 在这个过程中起协同作用。总的来说，LincR-PPP2R5C 缺失通过增加中性粒细胞的杀菌活性来减轻肺隐球菌病，这与 IL-4 水平的增加有关。本研究提供了宿主来源的 lncRNA 调节 感染的作用的具体证据。
肺隐球菌病是一种由 引起的人类真菌病，不仅在免疫功能低下的个体中常见，而且在免疫功能正常的患者中也常见。因此，研究肺隐球菌病的控制机制非常重要。在这里，我们证明了 LincR-PPP2R5C 的缺失导致中性粒细胞对 杀伤增加，从而减少肺部隐球菌感染。这些发现将极大地提高我们对 lncRNA 调节 发病机制的理解，促进 lncRNA 在肺隐球菌病治疗中的应用。
