Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
BC Centre for Disease Control, University of British Columbia, Vancouver, BC, Canada.
Front Immunol. 2022 Jul 7;13:858583. doi: 10.3389/fimmu.2022.858583. eCollection 2022.
Epstein-Barr virus (EBV) has been identified as a putative trigger of multiple sclerosis (MS). Previously, we reported that mice latently infected with murine gammaherpesvirus 68 (γHV-68), the murine homolog to EBV, and induced for experimental autoimmune encephalomyelitis (EAE), developed an enhanced disease more reminiscent of MS. These prior results showed that expression of CD40 on CD11bCD11c cells in latently infected mice was required to prime the strong Th1 response driving disease as well as decreasing Treg frequencies in the periphery and CNS. Subsequent work demonstrated that transfer of B cells from latently infected mice was sufficient to enhance disease. Herein, we show that B cells from infected mice do not need type I IFN signaling to drive a strong Th1 response, yet are important in driving infiltration of the CNS by CD8 T cells. Given the importance of type I IFNs in MS, we used IFNARko mice in order to determine if type I IFN signaling was important in the enhancement of EAE in latently infected mice. We found that while type I IFNs are important for the control of γHV-68 infection and maintenance of latency, they do not have a direct effect in the development of enhanced EAE.
EB 病毒（EBV）已被确定为多发性硬化症（MS）的潜在触发因素。此前，我们报告称，潜伏感染鼠γ疱疹病毒 68（γHV-68）的小鼠（EBV 的鼠同源物），以及诱导实验性自身免疫性脑脊髓炎（EAE），会发展出更类似于 MS 的增强疾病。这些先前的结果表明，潜伏感染小鼠中 CD11bCD11c 细胞上 CD40 的表达对于引发驱动疾病的强烈 Th1 反应以及降低外周血和中枢神经系统中的 Treg 频率是必需的。随后的工作表明，从潜伏感染小鼠中转移 B 细胞足以增强疾病。在此，我们表明感染小鼠的 B 细胞不需要 I 型 IFN 信号来驱动强烈的 Th1 反应，但对于 CD8 T 细胞浸润中枢神经系统很重要。鉴于 I 型 IFNs 在 MS 中的重要性，我们使用 IFNARko 小鼠来确定 I 型 IFN 信号是否在潜伏感染小鼠的 EAE 增强中很重要。我们发现，尽管 I 型 IFNs 对于控制 γHV-68 感染和维持潜伏很重要，但它们对增强型 EAE 的发展没有直接影响。
