Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes.
Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes.
复制标题
DOI：
10.3389/fimmu.2021.648184
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Liao F
中科院分区：
文献类型：
--
作者：
Lu MY;Lin YL;Kuo Y;Chuang CF;Wang JR;Liao F
肠道病毒71（EV 71）是一种来自小核糖核酸病毒科肠道病毒属的阳性单链RNA病毒。大多数感染EV 71的幼儿会出现轻微的手足口病症状，但有些会出现严重的神经系统症状。由EV 71感染引起的肢体瘫痪被认为主要是由脊髓中运动神经元的功能障碍引起的。然而，EV 71也靶向并损害骨骼肌，这也可能导致衰弱症状。在这项研究中，我们描绘了EV 71感染对骨骼肌的影响，使用小鼠模型。感染EV 71的小鼠幼仔在感染后第3天开始出现肢体瘫痪，并在感染后第5-7天达到高峰。后来，小鼠逐渐恢复，但不完全恢复。值得注意的是，严重的疾病与高水平的肌炎伴随着肌肉钙化和持续的运动终板异常。有趣的是，巨噬细胞表现出表型的动态变化，其中炎性巨噬细胞（CD 45 + CD 11b + Ly 6Chi）出现在感染的早期阶段，抗炎/恢复性巨噬细胞（CD 45 + CD 11b + Ly 6Clow/-）出现在晚期阶段。炎性巨噬细胞的存在与严重炎症相关，而恢复性巨噬细胞与恢复相关。总之，我们已经证明，EV 71感染引起肌炎，肌肉钙化和运动终板的结构缺陷。随后的肌肉再生与巨噬细胞表型的动态变化有关。
Enterovirus 71 (EV71) is a positive single-stranded RNA virus from the enterovirus genus of the Picornaviridae family. Most young children infected with EV71 develop mild symptoms of hand, foot and mouth disease, but some develop severe symptoms with neurological involvement. Limb paralysis from EV71 infection is presumed to arise mainly from dysfunction of motor neurons in the spinal cord. However, EV71 also targets and damages skeletal muscle, which may also contribute to the debilitating symptoms. In this study, we have delineated the impacts of EV71 infection on skeletal muscle using a mouse model. Mouse pups infected with EV71 developed limb paralysis, starting at day 3 post-infection and peaking at day 5-7 post-infection. At later times, mice recovered gradually but not completely. Notably, severe disease was associated with high levels of myositis accompanied by muscle calcification and persistent motor end plate abnormalities. Interestingly, macrophages exhibited a dynamic change in phenotype, with inflammatory macrophages (CD45+CD11b+Ly6Chi) appearing in the early stage of infection and anti-inflammatory/restorative macrophages (CD45+CD11b+Ly6Clow/-) appearing in the late stage. The presence of inflammatory macrophages was associated with severe inflammation, while the restorative macrophages were associated with recovery. Altogether, we have demonstrated that EV71 infection causes myositis, muscle calcification and structural defects in motor end plates. Subsequent muscle regeneration is associated with a dynamic change in macrophage phenotype.