Inhibition of the PD-1/PD-L1 signaling pathway enhances innate immune response of alveolar macrophages to mycobacterium tuberculosis in mice
Pulmonary Pharmacology & Therapeutics(2020)
摘要
Background: Mycobacterium tuberculosis (TB) is a pathogen that consequently leads to TB infection, which remains a significant global health concern. Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway is critical for terminating immune responses. The present study aimed to elucidate the regulatory role of the PD-1/PD-L1 signaling pathway in alveolar macrophages against Mycobacterium TB in mice. Methods: Specific pathogen free mice were initially prepared for Mycobacterium TB model establishment. The alveolar macrophages of the successfully modeled rats were evaluated to determine the levels of PD-1, PD-L1, AKT, mTOR, TNF-alpha, IL-2, IL-4, IL-6, IL-10, IL-17, IL-17A, and IFN-gamma. The surface makers of macrophages (CD11c, CD16, CD86, CD163, CD206, CX3CR-i and CSF-1R), level of ROS, apoptosis and cell cycle, were all assessed. Results: Elevated levels of PD -1 and PD -L1, decreased levels of AKT and mTOR, along with elevated levels of TNF-alpha, NF-kappa B, IL-17, IL-2, IL-6, IL-17A and IFN-gamma were identified in the alveolar macrophages infected with Mycobacterium TB, while an opposite trend was observed when PD-1/PD-L1 signaling pathway was inhibited. Additionally, elevated protein levels of CD11c, CD16 and CD86, as well as an increased rate of positive ROS and cell apoptosis, levels of Bax, and a diminished percentage of alveolar macrophages at the S and G2/M stages were detected in the event of Mycobacterium TB infection. A contrasting trend to the aforementioned findings was detected when the PD-1/PD-L1 signaling pathway was inhibited. Conclusion: Taken together, these results suggested that inhibition of the PD-1/PD-L1 signaling pathway enhanced the innate immune response of alveolar macrophages to Mycobacterium TB in mice.
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关键词
PD-1/PD-L1 signaling pathway,Alveolar macrophages,Immune regulation,Mycobacterium tuberculosis
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