Abstract:

Pseudomonas aeruginosa is a common pathogen. Interleukin-17 （IL-17） family cytokines are directly involved in the host immune response， which are key mediators of the defense against infection or inflammation in host. Using recombinant human IL-17 protein to treat Pseudomonas aeruginosa PAO1 and explore its invasive effect on lung epithelial cell A549， it was found that IL-17 can inhibit the invasion of PAO1 to A549 cells without affecting bacterial growth and cell proliferation. To explore the mechanism of IL-17 influencing PAO1 infection on host cells， we utilized transcriptome sequencing to analyze the changes of IL-17 on the PAO1 transcriptome. The results showed that there are 210 upregulated genes and 123 downregulated. GO functional analysis showed that the differential genes were mainly enriched in peptidase activity， protein binding and proteolysis. KEGG enrichment analysis showed that the differential genes were involved in RNA degradation， biofilm formation， microbial metabolism， ABC transport and carbon metabolism. In addition， the biofilm formation experiments further confirmed that IL-17 could reduce PAO1 biofilm formation. These findings provided a new idea and theoretical basis for the treatment of drug-resistant Pseudomonas aeruginosa in the treatment of related diseases caused by clinical infection.

Key words: Pseudomonas aeruginosa, infection, transcriptome, interleukin-17, lung epithelial cell

摘要：

铜绿假单胞菌是常见的致病菌，白细胞介素-17(interleukin-17，IL-17)家族细胞因子直接参与宿主免疫应答，是宿主防御感染或炎症的关键介质。利用重组人IL-17蛋白处理铜绿假单胞菌PAO1，探索其对肺上皮细胞A549的侵袭作用。结果发现，在不影响细菌生长和细胞增殖的情况下，IL-17能够抑制PAO1对A549细胞的入侵。利用转录组测序分析IL-17对PAO1转录组的改变，探索IL-17影响PAO1入侵宿主细胞的作用机制。结果表明，有210个差异基因表达上调，123个表达下调；GO功能分析显示差异基因主要富集在肽酶活性、蛋白结合和蛋白水解等方面；KEGG富集分析显示，差异基因涉及RNA降解、生物膜形成、微生物代谢、ABC转运以及碳代谢等通路。此外，生物膜形成实验进一步证实了IL-17能够降低PAO1生物膜的形成。研究结果为耐药铜绿假单胞菌在临床感染造成的相关疾病的治疗提供了新思路和理论基础。

关键词: 铜绿假单胞菌, 感染, 转录组, 白细胞介素-17, 肺上皮细胞