铜绿假单胞菌是院内常见的条件致病菌，该类肺炎患者的临床预后与其免疫状态密切相关。研究表明宿主细胞的功能与体内共生菌密切相关，也证实肺内存在共生菌影响着免疫细胞的功能。我们的研究证实γδT-17细胞通过产IL-17在该类肺炎中发挥保护作用，也发现死亡患者肺内IL-17表达不足且肺内正常共生菌柯林斯菌属的比例显著下降。我们的小鼠实验发现吸入促柯林斯菌生长的鼠李糖乳杆菌能恢复肺内IL-17表达，改善预后，提示了柯林斯菌属可能对γδT-17细胞具有影响，但机制不明确。因此，本课题拟①确认肺内菌群变化与细胞功能相关的临床现象；②在该类感染模型中正反调节肺内柯林斯菌属比例，阐明该菌属的下降可导致肺内γδT-17 细胞产IL-17功能受损，恶化预后；上调该菌属比例可维护该细胞功能，改善预后。③调控CD1d/微生物脂质，探索该菌群影响免疫细胞功能的机制。本课题立足于免疫调节，探究改善该类感染预后的新策略。

Pseudomonas aeruginosa is a common conditional pathogen in the hospital acquired infections. The clinical prognosis of Pseudomonas aeruginosa pneumonia mainly depends on patient immune status. The human body contains approximately ten times as many bacterial cells as human cells. Known as commensal bacteria, they exist in a mutually beneficial, symbiotic relationship with their human hosts.Previous studies have focused on how bacteria shape and protect the immune system within the intestines, it is becoming clear that pulmonary also benefit from commensal bacteria.Our previous studies showed that interleukin17-producing γδT cells (γδT-17 cells) have a protective effect on both innate immunity and humoral immunity via IL-17 during acute pulmonary Pseudomonas aeruginosa infection. We also found that the IL-17 protein level from low respiratory tract in the death Pseudomonas aeruginosa pneumonia patients was significantly decreased than the survival patients. Meanwhile, the relatively abundance of Collinsella in the lung microbiome was obviously lower in the death patients. Our animal experiments suggested that LGG inhalation which may rescue the relatively abundance of Collinsella, increased the IL-17 protein level in the lung and improved the clinical prognosis in the acute pulmonary Pseudomonas aeruginosa infection mice. To explore the role of the lung microbiome play on the pulmonary resident γδT-17 cells homeostasis during Pseudomonas aeruginosa pneumonia. We plan to ①design a clinical trial to validate the level of IL-17 produced by γδT-17 cells and the number of γδT-17 cells are significantly decreased in the Pseudomonas aeruginosa pneumonia patients with poor prognosis and it has a powerful relationship with the relatively abundance of Collinsella in the lung microbiome. ②identificate decreased the relatively abundance of Collinsella in the lung microbiome could impair the function γδ-T17 cells and the lower level of IL-17 in lung may worse the clinical prognosis in the infection mice model. After rescued the relatively abundance of Collinsella in the lung may maintain the homeostasis of pulmonary resident γδT-17 cells and may improve the prognosis. ③investigate whether the role of the lung microbiome play on the pulmonary resident γδT-17 cells homeostasis during Pseudomonas aeruginosa pneumonia is in a lipid antigen/CD1d dependent manner. Our project is based on host immunoregulation and try to explore a new strategy to improve the prognosis of Pseudomonas aeruginosa pneumonia patients.