PD-1调控TREM-1/TREM-2偏移介导巨噬细胞焦亡在脓毒症免疫抑制中的作用研究

单核/巨噬细胞是脓毒症固有免疫应答中识别和清除病原体的关键抗感染细胞。但在脓毒症晚期，巨噬细胞由以杀灭病原微生物为主的M1型向以免疫调节为主的M2型转变——释放促炎因子下降，抑炎因子增多，吞噬能力下降，自身凋亡，介导脓毒症后期免疫抑制状态。最新研究显示，免疫球蛋白超家族受体TREM-1和TREM-2在炎症反应中发挥重要的作用，TREM-1介导的细胞焦亡作用参与炎症性疾病的发生发展。PD-1是重要的负性共刺激分子，巨噬细胞中PD-1/PD-L1通路是否调控TREM-1/-2的平衡表达，诱导促炎性的TREM-1向抑炎性的TREM-2转化，抑制细胞焦亡过程，介导巨噬细胞由M1型向M2型趋化，导致免疫抑制状态影响患者预后引起我们的关注。本研究拟揭示PD-1调控TREM-1/-2偏移介导巨噬细胞焦亡作用，诱导巨噬细胞M1型向M2型趋化参与脓毒症免疫抑制的机制，为寻找新的诊断和治疗靶点提供依据。

Monocytes/macrophages are key infection-fighting cells in the innate immune response to sepsis to identify and clear pathogens. However, in the late stage of sepsis, macrophages are transformed from the M1-type, which mainly kills pathogenic microorganisms, to the M2-type, which is dominated by immune regulation. The release of pro-inflammatory factors is decreased, anti-inflammatory factors are increased, phagocytic capacity is decreased, and self-apoptosis occurs, which mediates the immunosuppressive state in the later stage of sepsis. Recent studies have shown that the immunoglobulin superfamily receptors TREM-1 and TREM-2 play an important role in inflammation, and TREM-1 mediated pyroptosis is involved in the occurrence and development of inflammatory diseases. PD-1 is an important negative stimulus molecule, whether the PD-1/PD-L1 pathway in macrophages influence the balance of TREM-1/TREM-2 expression, induction of promoting inflammatory TREM-1 to suppressed inflammatory TREM-2 transformation, mediating macrophage polarization, affect the prognosis of patients with sepsis cause our attention. This study intends to evaluate the role of PD-1 in regulating the migration of TREM-1/TREM-2 to mediate the pyroptosis of macrophages, so as to inhibit M1-type macrophage polarization and promote M2-type macrophage polarization to participate in sepsis immunosuppression. This study will provide new theoretical basis and for the treatment of sepsis.