Institute of Pathogenic Biology, Hengyang Medical College, University of South China, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, Hunan 421001, China.
Institute of Pathogenic Biology, Hengyang Medical College, University of South China, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, Hunan 421001, China.
Biochim Biophys Acta Mol Cell Res. 2022 Oct;1869(10):119324. doi: 10.1016/j.bbamcr.2022.119324. Epub 2022 Jul 6.
Although the protective effects of Chlamydia psittaci plasmid-encoded protein CPSIT_P7 as vaccine antigens to against chlamydial infection have been confirmed in our previous study, the function and mechanism of CPSIT_P7 inducing innate immunity in the antibacterial response remain unknown. Here, we found that plasmid protein CPSIT_P7 could induce M1 macrophage polarization upregulating the genes of the surface molecule CD86, proinflammatory cytokines (TNF-α, IL-6, and IL-1β), and antibacterial effector NO synthase 2 (iNOS). During M1 macrophage polarization, macrophages acquire phagocytic and microbicidal competence, which promotes the host antibacterial response. As we observed that CPSIT_P7-induced M1 macrophages could partially reduce the infected mice pulmonary Chlamydia psittaci load. Furthermore, CPSIT_P7 induced M1 macrophage polarization through the TLR4-mediated MAPK and NF-κB pathways. Collectively, our results highlight the effect of CPSIT_P7 on macrophage polarization and provide new insights into new prevention and treatment strategies for chlamydial infection.
虽然我们之前的研究已经证实鹦鹉热衣原体质粒编码蛋白 CPSIT_P7 作为疫苗抗原对衣原体感染具有保护作用，但 CPSIT_P7 诱导固有免疫在抗菌反应中的功能和机制仍不清楚。在这里，我们发现质粒蛋白 CPSIT_P7 可以诱导 M1 巨噬细胞极化，上调表面分子 CD86、促炎细胞因子（TNF-α、IL-6 和 IL-1β）和抗菌效应物一氧化氮合酶 2（iNOS）的基因。在 M1 巨噬细胞极化过程中，巨噬细胞获得吞噬和杀菌能力，从而促进宿主的抗菌反应。正如我们观察到的，CPSIT_P7 诱导的 M1 巨噬细胞可以部分降低感染小鼠肺部鹦鹉热衣原体的负荷。此外，CPSIT_P7 通过 TLR4 介导的 MAPK 和 NF-κB 途径诱导 M1 巨噬细胞极化。总之，我们的结果强调了 CPSIT_P7 对巨噬细胞极化的影响，并为衣原体感染的新的预防和治疗策略提供了新的见解。
