Department of Laboratory Medicine and.
Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, China; and.
Am J Respir Cell Mol Biol. 2020 Jun;62(6):760-766. doi: 10.1165/rcmb.2019-0391OC.
Invasive pulmonary aspergillosis is a life-threatening disease, particularly in immunocompromised patients, despite currently available therapy. IL-27 is an important regulatory cytokine in infection and immunity. However, its role in the pathogenesis of invasive pulmonary aspergillosis remains unknown. Here we found that pulmonary infection induced an elevated production of IL-27 in the lung. As compared with wild-type (WT) mice, IL-27R (IL-27 receptor)-deficient mice developed less severe infection when challenged with conidia, as evidenced by the decreased fungal colonization and pathology of lungs and the increased survival. IL-27R deficiency led to significantly higher production of IFN-γ in the lung after infection, and the increased resistance to invasive pulmonary infection in IL-27R-deficient mice was ablated by neutralizing IFN-γ. Importantly, neutralization of IL-27 could protect WT mice against invasive pulmonary infection. Our data therefore suggest an important role of IL-27 in impairing anti- host immunity, which may have translational implications in treating clinical cases of invasive pulmonary aspergillosis
侵袭性肺曲霉病是一种危及生命的疾病，尤其是在免疫功能低下的患者中，尽管目前有可用的治疗方法。IL-27 是感染和免疫中一种重要的调节细胞因子。然而，它在侵袭性肺曲霉病发病机制中的作用尚不清楚。在这里，我们发现肺部感染会导致肺部 IL-27 的产生增加。与野生型（WT）小鼠相比，用分生孢子攻击时，IL-27R（IL-27 受体）缺陷型小鼠的感染程度较轻，表现为肺部真菌定植和病理学减少，存活率增加。IL-27R 缺陷导致感染后肺部 IFN-γ 的产生显著增加，而中和 IFN-γ 可消除 IL-27R 缺陷型小鼠对侵袭性肺感染的抵抗力。重要的是，IL-27 的中和可保护 WT 小鼠免受侵袭性肺感染。因此，我们的数据表明 IL-27 在损害宿主免疫方面起着重要作用，这可能对治疗侵袭性肺曲霉病的临床病例具有转化意义。
