Wang Chong, Zhang Nan, Qi Luting, Yuan Jiaolong, Wang Ke, Wang Kunlun, Ma Sicong, Wang Haili, Lou Wenjuan, Hu Pingdong, Awais Muhammad, Cao Shengbo, Fu Zhen F, Cui Min
State Key Laboratory of Agricultural Microbiology, Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; and.
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
J Immunol. 2017 Nov 1;199(9):3094-3105. doi: 10.4049/jimmunol.1700671. Epub 2017 Oct 4.
Resolution of viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. In this study, we examined Japanese encephalitis virus (JEV) infection leading to acute encephalopathy depending on suppression of the adaptive immune responses mediated by innate cells. Infection with P3 strains of JEV enhanced myeloid-derived suppressor cell (MDSC) populations, and the survival rate of JEV-infected mice improved after MDSC depletion. Mechanically, P3-induced MDSCs suppressed CD4 T cell immune responses, especially responses of T follicular helper (Tfh) cells, leading to decreased splenic B cells (CD19) and blood plasma cells (CD19CD138) and reduced levels of total IgM and JEV-specific neutralizing Abs. Upon depleting P3-induced MDSCs in vivo, the Tfh cell population, B cells, plasma cells, and Ab production recovered. These findings provide unique insights regarding MDSC functions in mediating immune suppression via inhibiting Tfh cell responses and further impairing humoral immunity, which facilitate the progression of infection.
病毒感染的清除需要激活先天细胞以启动和维持适应性免疫反应。在本研究中，我们研究了日本脑炎病毒（JEV）感染导致急性脑病的情况，这取决于先天细胞介导的适应性免疫反应的抑制。用JEV的P3毒株感染可增加髓系来源的抑制性细胞（MDSC）群体，在MDSC耗竭后，JEV感染小鼠的存活率提高。从机制上讲，P3诱导的MDSC抑制CD4 T细胞免疫反应，特别是滤泡辅助性T（Tfh）细胞的反应，导致脾脏B细胞（CD19）和血浆细胞（CD19CD138）减少，以及总IgM和JEV特异性中和抗体水平降低。在体内耗尽P3诱导的MDSC后，Tfh细胞群体、B细胞、浆细胞和抗体产生得以恢复。这些发现为MDSC通过抑制Tfh细胞反应介导免疫抑制并进一步损害体液免疫从而促进感染进展的功能提供了独特的见解。
