Laboratory of Immunology and Vaccinology, Faculty of Veterinary Medicine, FARAH, ULiège, Liège 4000, Belgium.
Laboratory of Biology of Tumor and Development, GIGA-Cancer ULiège and "Centre Hospitalier Universitaire de Liège (CHU)", Liège 4000, Belgium.
Sci Immunol. 2022 Jul 15;7(73):eabn3240. doi: 10.1126/sciimmunol.abn3240.
Gammaherpesviruses (γHVs) have coevolved with their host, leading to a remarkably high infection prevalence and establishment of latency. The lifelong persistence of γHVs in hosts appears to broadly shape host immunity, and we show here that pulmonary infection with Murid herpesvirus 4 (MuHV-4), a mouse γHV, drives the recruitment of Ly6C monocytes (MOs) into the airway, thereby modulating the host immune response. The absence of Ly6C MOs is associated with severe virus-induced immunopathology and the systemic release of inflammatory mediators. Mechanistically, MuHV-4-imprinted MOs recruit CD4 T cells to the airways and trigger immunosuppressive signaling pathways through the PD-L1/PD-1 axis, thereby dampening the deleterious activation of cytotoxic CD4 T cells. These results uncover a role for Ly6C MOs in modulating CD4 T cell functions and reveal pathways that could be targeted therapeutically to reduce detrimental immunopathological responses associated with respiratory viral infections.
γ 疱疹病毒（γHVs）与宿主共同进化，导致其感染率极高且潜伏期长。γHVs 在宿主体内的终身存在似乎广泛影响宿主的免疫功能，我们在这里表明，肺部感染鼠疱疹病毒 4（MuHV-4），一种小鼠 γHV，会促使 Ly6C 单核细胞（MOs）招募到气道中，从而调节宿主的免疫反应。缺乏 Ly6C MOs 与严重的病毒诱导免疫病理学和炎症介质的全身释放有关。从机制上讲，MuHV-4 印记的 MOs 通过 PD-L1/PD-1 轴将 CD4 T 细胞招募到气道，并触发免疫抑制信号通路，从而抑制细胞毒性 CD4 T 细胞的有害激活。这些结果揭示了 Ly6C MOs 在调节 CD4 T 细胞功能中的作用，并揭示了可以通过靶向治疗来减轻与呼吸道病毒感染相关的有害免疫病理反应的途径。
