Zhan Xiaoxia, Jiang Xiaobing, He Qiuying, Zhong Liangyin, Wang Yichong, Huang Yulan, He Shitong, Sheng Junli, Liao Jianwei, Zeng Zhijie, Hu Shengfeng
Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Cent Eur J Immunol. 2022;47(1):30-40. doi: 10.5114/ceji.2022.113086. Epub 2022 Feb 11.
Chronic inflammation develops when the immune system is unable to clear a persistent insult. Unresolved chronic inflammation leads to immunosuppression to maintain the internal homeostatic conditions, which is mediated primarily by myeloid-derived suppressor cells (MDSCs). Toll-like receptors 2 (TLR2) has an important role in chronic inflammation and can be activated by a vast number and diversity of TLR2 ligands, for example Pam2CSK4. However, the regulatory effect of TLR2 signaling on MDSCs in chronic inflammation remains controversial. This study demonstrated that heat-killed Mycobacterium bovis BCG-induced pathology-free chronic inflammation triggered suppressive monocytic MDSCs (M-MDSCs) that expressed TLR2. Activation of TLR2 signaling by Pam2CSK4 treatment enhanced immunosuppression of M-MDSCs by upregulating inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production partly through signal transducer and activator of transcription 3 (STAT3) activation. Thus, TLR2 has a fundamental role in promoting the MDSC-mediated immunosuppressive environment during chronic inflammation and might represent a potentially therapeutic target in chronic inflammation disease.
当免疫系统无法清除持续性损伤时，慢性炎症就会发生。未解决的慢性炎症会导致免疫抑制以维持体内稳态，这主要由髓源性抑制细胞（MDSCs）介导。Toll样受体2（TLR2）在慢性炎症中起重要作用，并且可被大量不同的TLR2配体激活，例如Pam2CSK4。然而，TLR2信号传导在慢性炎症中对MDSCs的调节作用仍存在争议。本研究表明，热灭活的牛分枝杆菌卡介苗诱导的无病理慢性炎症触发了表达TLR2的抑制性单核细胞MDSCs（M-MDSCs）。通过Pam2CSK4处理激活TLR2信号传导，部分通过信号转导和转录激活因子3（STAT3）激活，上调诱导型一氧化氮合酶（iNOS）活性和一氧化氮（NO）生成，从而增强了M-MDSCs的免疫抑制作用。因此，TLR2在慢性炎症过程中促进MDSC介导的免疫抑制环境方面具有重要作用，可能是慢性炎症性疾病的一个潜在治疗靶点。
