2. Academic Validation
  3. Absence of PD-L1 signaling hinders macrophage defense against Mycobacterium tuberculosis via upregulating STAT3/IL-6 pathway

Absence of PD-L1 signaling hinders macrophage defense against Mycobacterium tuberculosis via upregulating STAT3/IL-6 pathway

  • Microbes Infect. 2024 May 8:105352. doi: 10.1016/j.micinf.2024.105352.
Peijie Qu 1,  Xinyu Li 2,  Weihuang Liu 3,  Fangting Zhou 4,  Xiaoxu Xu 4,  Jun Tang 2,  Mengmeng Sun 2,  Junli Li 2,  Haifeng Li 2,  Yunlin Han 2,  Chengjun Hu 4,  Yueshan Lei 4,  Qin Pan 5,  Lingjun Zhan 6
Affiliations

Affiliations

  • 1 Department of Anatomy, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China; Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 2 Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 3 Medical Research Center for Structural Biology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China.
  • 4 Department of Anatomy, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China.
  • 5 Department of Anatomy, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China. Electronic address: panqincn@whu.edu.cn.
  • 6 Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: Zhanlj@cnilas.org.
PMID: 38729294 DOI: 10.1016/j.micinf.2024.105352
Abstract

The blockade of programmed death-ligand 1 (PD-L1) pathway has been clinically used in Cancer Immunotherapy, while its effects on infectious diseases remain elusive. Roles of PD-L1 signaling in the macrophage-mediated innate immune defense against M.tb is unclear. In this study, the outcomes of tuberculosis (TB) in wild-type (WT) mice treated with anti-PD-1/PD-L1 therapy and macrophage-specific Pdl1-knockout (Pdl1ΔΜΦ) mice were compared. Treatment with anti-PD-L1 or anti-PD-1 benefited protection against M.tb Infection in WT mice, while Pdl1ΔΜΦ mice exhibited the increased susceptibility to M.tb Infection. Mechanistically, the absence of PD-L1 signaling impaired M.tb killing by macrophages. Furthermore, elevated STAT3 activation was found in PD-L1-deficient macrophages, leading to increased interleukin (IL)-6 production and reduced inducible nitric oxide synthase (iNOS) expression. Inhibiting STAT3 phosphorylation partially impeded the increase in IL-6 production and restored iNOS expression in these PD-L1-deficient cells. These findings provide valuable insights into the complexity and mechanisms underlying anti-PD-L1 therapy in the context of tuberculosis.

Keywords

Macrophages; Mycobacterium tuberculosis; PD-L1 signaling; STAT3/IL-6 pathway.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15146
    98.64%, STAT3 Inhibitor