Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan.
Front Immunol. 2021 Feb 18;11:614743. doi: 10.3389/fimmu.2020.614743. eCollection 2020.
Enterovirus 71 (EV71) is a positive single-stranded RNA (ssRNA) virus from the enterovirus genus of family and causes diseases ranged from the mild disease of hand, foot and mouth disease (HFMD) to the severe disease of neurological involvement in young children. TLR7 is an intracellular pattern recognition receptor (PRR) recognizing viral ssRNA. In this study, we investigated the role of TLR7 in EV71 infection in mouse pups (10-12 days old) and found that wild-type (WT) and TLR7 knock-out (TLR7KO) mice infected with EV71 showed similar limb paralysis at the onset and peak of the disease, comparable loss of motor neurons, and similar levels of antiviral molecules in the spinal cord. These results suggest that TLR7 is not the absolute PRR for EV71 in the spinal cord. Interestingly, TLR7KO mice infected with EV71 exhibited significantly delayed recovery from limb paralysis compared with WT mice. TLR7KO mice infected with EV71 showed significantly decreased levels of IgM and IgG2, important antibodies for antiviral humoral immunity. Furthermore, TLR7KO mice infected with EV71 showed a decrease of germinal center B cells in the spleen compared with WT mice. Altogether, our study suggests that TLR7 plays a critical role in anti-viral humoral immunity rather than in being a PRR in the spinal cord during EV71 infection in young mice.
肠道病毒 71 型（EV71）是一种正链单链 RNA（ssRNA）病毒，属于肠道病毒科，可引起从手、足、口病（HFMD）轻症到小儿神经受累重症等多种疾病。Toll 样受体 7（TLR7）是一种识别病毒 ssRNA 的细胞内模式识别受体（PRR）。在本研究中，我们研究了 TLR7 在感染 EV71 的 10-12 日龄小鼠幼仔中的作用，发现野生型（WT）和 TLR7 敲除（TLR7KO）小鼠在疾病的发病和高峰时表现出相似的肢体麻痹，运动神经元丧失相当，脊髓中抗病毒分子水平相似。这些结果表明 TLR7 不是 EV71 在脊髓中的绝对 PRR。有趣的是，与 WT 小鼠相比，感染 EV71 的 TLR7KO 小鼠从肢体麻痹中恢复明显延迟。感染 EV71 的 TLR7KO 小鼠的 IgM 和 IgG2 水平显著降低，IgM 和 IgG2 是抗病毒体液免疫的重要抗体。此外，感染 EV71 的 TLR7KO 小鼠的脾脏生发中心 B 细胞数量明显减少，而 WT 小鼠则无此现象。综上所述，本研究表明 TLR7 在抗 EV71 感染的抗病毒体液免疫中发挥关键作用，而不是在感染 EV71 的幼鼠脊髓中作为 PRR。
