2. Academic Validation
  3. TLR9 promotes monocytic myeloid-derived suppressor cell induction during JEV infection

TLR9 promotes monocytic myeloid-derived suppressor cell induction during JEV infection

  • Microbes Infect. 2024 May 7:105336. doi: 10.1016/j.micinf.2024.105336.
Tingting Lian 1,  Weijia Zhang 1,  Haoran Su 1,  Qing Yu 1,  Hongxin Zhang 1,  Qingcui Zou 1,  Haowei Chen 1,  Wenjing Xiong 1,  Nan Zhang 1,  Ke Wang 1,  Ling Zhao 1,  Zhen F Fu 1,  Min Cui 2
Affiliations

Affiliations

  • 1 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan 430070, China; International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan 430070, China.
  • 2 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan 430070, China; International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan 430070, China. Electronic address: cuimin@mail.hzau.edu.cn.
PMID: 38724001 DOI: 10.1016/j.micinf.2024.105336
Abstract

Myeloid-derived suppressor cells (MDSCs) are a group of heterologous populations of immature bone marrow cells consisting of progenitor cells of macrophages, dendritic cells and granulocytes. Recent studies have revealed that the accumulation of MDSCs in the mouse spleen plays a pivotal role in suppressing the immune response following JEV Infection. However, the mechanisms by which JEV induces MDSCs are poorly understood. Here, it was found that JEV Infection induces mitochondrial damage and the release of mitochondrial DNA (mtDNA), which further leads to the activation of TLR9. TLR9 deficiency decreases the M-MDSCs population and their suppressive function both in vitro and in vivo. Moreover, the increase of MHCⅡ expression on antigen-presenting cells and CD28 expression on T cells in TLR9-/- mice was positively correlated with M-MDSCs reduction. Accordingly, the survival rate of TLR9-/- mice dramatically increased after JEV Infection. These findings reveal the connections of mitochondrial damage and TLR9 activation to the induction of M-MDSCs during JEV Infection.

Keywords

JEV; M-MDSCs; TLR9.

Figures
Products