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

Zijing Guo,Zhidong Zhang,Yin Zhao,Yanmin Li

doi:10.3390/v13122358

Abstract

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.

Highlights

Foot-and-mouth disease (FMD) is recognized as one of the most infectious and economically important diseases of domestic livestock [1]
FMD virus (FMDV) Infection Was Lethal to C57BL/6 Mice
The results showed that the apoptosis of CD3+ T cells was increased in FMDV-infected mice at 48 and 60 hpi (66.6 ± 6.7% and 66. 3 ± 5.9%, n = 3, p = 0.0018 and p = 0.0020, respectively) when compared with the mock mice (27.4 ± 0.5%, n = 3) and, among the late apoptosis of CD3+ T cells, was significantly increased in FMDV-infected mice at 48 and 60 hpi (47.1 ± 7.5% and 45.6 ± 6.6%, n = 3, p = 0.0007 and p = 0.0013, respectively) when compared with the mock mice (17 ± 0.5%, n = 3) (Figure 3A,D)

Summary

Introduction

FMD is recognized as one of the most infectious and economically important diseases of domestic livestock [1]. The etiological agent, FMD virus (FMDV), an aphthovirus of the Picornaviridae family, can infect a multitude of cloven-hoofed animal species, including both ruminants and suids [1,2]. Following FMDV infection, lymphocyte depletion in the peripheral blood, referred to as lymphopenia, is a common characteristic in pigs [3,4], cattle [5,6], and C57BL/6 mice [7]. Lymphopenia is considered to be one of the important mechanisms by which the FMDV evade the host immune response and cause immune suppression [2,8]. The mechanisms of lymphopenia caused by FMDV are still unclear. A previous study reported that FMDV serotype C can directly infect T and B cells in lymphoid compartments of swine, which may result in lymphoid depletion [4].

Methods

Results

Conclusion