Nady Soad, Abdel-Rahman Mona, Sousa Silvia A, LEITãO Jorge H, Morad Mostafa, El-Hennamy Rehab E
Department of Zoology and Entomology, Faculty of Science, Helwan University, Helwan, Egypt.
Department of Bioengineering, IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.
Cent Eur J Immunol. 2019;44(4):403-413. doi: 10.5114/ceji.2019.92800. Epub 2020 Jan 20.
T helper 17 cells are involved in the immunopathology of cystic fibrosis. They play a key role in recruitment of neutrophils, which is the first line of defence against bacteria. Additionally, Burkholderia cenocepacia outer membrane protein A (OmpA) BCAL2958 is considered a potential protective epitope for vaccine development. The present study aimed to investigate the neutrophil response to OmpA in the presence of Th17 cytokines, IL-17 and IL-22 at different times of activation. Neutrophils were isolated from whole blood of healthy volunteers and activated with OmpA in the presence of IL-17, IL-22 or both cytokines together. Supernatant was collected after 1 h, 2 h, 4 h, 8 h, and 12 h. Neutrophil activation was assessed by measuring MPO, TNF-, elastase, hydrogen peroxide, catalase and NO. The results revealed that the combination of IL-17 and IL-22 cytokines induced the release of NE, catalase, HO and TNF- from neutrophils activated with Burkholderia OmpA at late stages of activation. However, IL-22 alone or IL-17 alone decreased the myeloperoxidase (MPO), catalase and NE levels at early stages of neutrophil activation. The presence of IL-17 alone led to a significant increase in TNF- level after 1 h and 12 h. However, the presence of IL-22 alone led to a significant increase in TNF- level after only 1 h but a significant decrease after 8 h of activation was observed as compared to OmpA stimulated neutrophils. In conclusion, Th17 cytokines IL-17 and IL-22, have differential effects during the neutrophil response to Burkholderia OmpA.
辅助性T细胞17参与囊性纤维化的免疫病理学过程。它们在招募中性粒细胞中起关键作用,而中性粒细胞是抵御细菌的第一道防线。此外,洋葱伯克霍尔德菌外膜蛋白A(OmpA)BCAL2958被认为是疫苗开发的潜在保护性表位。本研究旨在调查在不同激活时间下,在辅助性T细胞17细胞因子白细胞介素-17(IL-17)和白细胞介素-22(IL-22)存在的情况下,中性粒细胞对OmpA的反应。从健康志愿者的全血中分离出中性粒细胞,并在IL-17、IL-22或两种细胞因子共同存在的情况下用OmpA进行激活。在1小时、2小时、4小时、8小时和12小时后收集上清液。通过测量髓过氧化物酶(MPO)、肿瘤坏死因子-α(TNF-α)、弹性蛋白酶、过氧化氢、过氧化氢酶和一氧化氮来评估中性粒细胞的激活情况。结果显示,在激活后期,IL-17和IL-22细胞因子的组合诱导了被洋葱伯克霍尔德菌OmpA激活的中性粒细胞释放中性粒细胞弹性蛋白酶(NE)、过氧化氢酶、过氧化氢(HO)和TNF-α。然而,单独的IL-22或单独的IL-17在中性粒细胞激活早期会降低髓过氧化物酶(MPO)、过氧化氢酶和NE水平。单独存在IL-17会导致1小时和12小时后TNF-α水平显著升高。然而,单独存在IL-22仅在1小时后导致TNF-α水平显著升高,但与OmpA刺激的中性粒细胞相比,在激活8小时后观察到显著降低。总之,辅助性T细胞17细胞因子IL-17和IL-22在中性粒细胞对洋葱伯克霍尔德菌OmpA的反应过程中具有不同的作用。