Journal Article

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

Li, Yanmin, Zhang, Zhidong, Zhao, Yin, Guo, Zijing

2021

Overview

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-1β, TNF-α, IFN-α/β, TGF-β, 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.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Antibodies / Apoptosis / B-Lymphocytes - immunology / blood serum / CD223 antigen / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / Cell growth / Cloning / co-inhibitory molecules / CTLA-4 protein / Cytokines / Cytokines - immunology / disease severity / Flow cytometry / Foot & mouth disease / foot-and-mouth disease / Foot-and-Mouth Disease - virology / Foot-and-mouth disease virus / Foot-and-Mouth Disease Virus - immunology / IL-1β / Infections / Interleukin 10 / Interleukin 17 / Interleukin 18 / Interleukin 2 / Interleukin 6 / Interleukin-10 - genetics / Interleukin-10 - immunology / Killer Cells, Natural - immunology / Laboratories / Lymphocyte Count / Lymphocytes / Lymphocytes B / Lymphocytes T / Lymphopenia / Lymphopenia - immunology / Lymphopenia - virology / Mice / Mice, Inbred C57BL / Mice, Knockout / Peripheral blood / Reagents / serotypes / Signal Transduction / therapeutics / trafficking / Tumor necrosis factor-α / Viral infections / α-Interferon