Interleukin-10-Mediated Lymphopenia Caused by Acute Infection with Foot-and-Mouth Disease Virus in Mice

文献类型： 外文期刊

第一作者： Guo, Zijing

作者： Guo, Zijing;Zhao, Yin;Guo, Zijing;Zhang, Zhidong;Li, Yanmin

作者机构：

关键词： foot-and-mouth disease virus; lymphopenia; interleukin-10; apoptosis; trafficking; co-inhibitory molecules

期刊名称：VIRUSES-BASEL （ 影响因子：5.818； 五年影响因子：5.811 ）

ISSN：

年卷期： 2021 年 13 卷 12 期

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收录情况： SCI

摘要： Foot-and-mouth disease (FMD) is characterized by a pronounced lymphopenia that is associated with immune suppression. However, the mechanisms leading to lymphopenia remain unclear. In this study, the number of total CD4(+), CD8(+) T cells, B cells, and NK cells in the peripheral blood were dramatically reduced in C57BL/6 mice infected with foot-and-mouth disease virus (FMDV) serotype O, and it was noted that mice with severe clinical symptoms had expressively lower lymphocyte counts than mice with mild or without clinical symptoms, indicating that lymphopenia was associated with disease severity. A further analysis revealed that lymphocyte apoptosis and trafficking occurred after FMDV infection. In addition, coinhibitory molecules were upregulated in the expression of CD4(+) and CD8(+) T cells from FMDV-infected mice, including CTLA-4, LAG-3, 2B4, and TIGIT. Interestingly, the elevated IL-10 in the serum was correlated with the appearance of lymphopenia during FMDV infection but not IL-6, IL-2, IL-17, IL-18, IL-1 beta, TNF-alpha, IFN-alpha/beta, TGF-beta, and CXCL1. Knocking out IL-10 (IL-10(-/-)) mice or blocking IL-10/IL-10R signaling in vivo was able to prevent lymphopenia via downregulating apoptosis, trafficking, and the coinhibitory expression of lymphocytes in the peripheral blood, which contribute to enhance the survival of mice infected with FMDV. Our findings support that blocking IL-10/IL-10R signaling may represent a novel therapeutic approach for FMD.

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