Department of Pulmonary and Critical Care Medicine, the Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, Guangdong, China.
Department of Pulmonary and Critical Care Medicine, the Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, Guangdong, China.
Infect Genet Evol. 2020 Dec;86:104582. doi: 10.1016/j.meegid.2020.104582. Epub 2020 Oct 2.
Methicillin-resistant Staphylococcus aureus (MRSA) carrying Panton-Valentine leukocidin, a pore-forming toxin, is a common cause of necrotizing pneumonia. However, the early pulmonary inflammatory response following PVL(+) MRSA infection is unknown. The purpose of this study was to use a murine model to determine the effect of PVL(+) MRSA on lung tissues and the expression of cytokines and JAK and STAT mRNA and protein.
Mice were randomly divided into 3 groups and intra-nasally treated with PBS (control group), recombinant PVL (rPVL group), and PVL(+) MRSA (PVL group). At 24 and 48 h after inoculation, bronchoalveolar lavage fluid (BALF) was tested for cytokine levels, and lung tissues were tested for JAK and STAT mRNA and protein expression, and examined after hematoxylin and eosin staining.
Mice infected with the PVL(+) strain became ill, characterized by impaired mobility, hunched posture, ruffled fur, and labored breathing. Lung tissue exhibited tissue necrosis and hemorrhage. BALF levels of IL-8, TNF-α, IFN-γ, IL-12, sICAM-1, and sVCAM-1 were increased in the rPVL or PVL groups, while levels of IL-10 and IL-4 levels were similar among the groups. JAK1 and STAT1 mRNA expression and protein levels were increased in lung tissue from mice infected with PVL(+) MRSA and rPVL.
PVL is a significant S. aureus virulence factor, and upregulates the expression of proinflammatory cytokines but does not affect the expression of anti-inflammatory cytokines. The effect of PVL may be due to JAK/STAT pathway activation. Blockade of the JAK/STAT pathway may decrease the severity of PVL(+) MRSA pneumonia.
携带细胞毒素 Panton-Valentine 白细胞溶解素（一种形成孔的毒素）的耐甲氧西林金黄色葡萄球菌（MRSA）是坏死性肺炎的常见原因。然而，PVL(+)MRSA 感染后的早期肺部炎症反应尚不清楚。本研究旨在使用小鼠模型来确定 PVL(+)MRSA 对肺组织和细胞因子以及 JAK 和 STAT mRNA 和蛋白表达的影响。
将小鼠随机分为 3 组，通过鼻腔内给予 PBS（对照组）、重组 PVL（rPVL 组）和 PVL(+)MRSA（PVL 组）。接种后 24 和 48 小时，检测支气管肺泡灌洗液（BALF）中的细胞因子水平，并检测肺组织中 JAK 和 STAT mRNA 和蛋白表达，以及苏木精和伊红染色后的检查。
感染 PVL(+)株的小鼠出现疾病，表现为运动能力下降、弓背、毛发蓬乱和呼吸困难。肺组织出现组织坏死和出血。rPVL 或 PVL 组 BALF 中 IL-8、TNF-α、IFN-γ、IL-12、sICAM-1 和 sVCAM-1 水平升高，而各组间 IL-10 和 IL-4 水平相似。PVL(+)MRSA 和 rPVL 感染小鼠的肺组织中 JAK1 和 STAT1 mRNA 表达和蛋白水平增加。
PVL 是金黄色葡萄球菌的重要毒力因子，上调促炎细胞因子的表达，但不影响抗炎细胞因子的表达。PVL 的作用可能是由于 JAK/STAT 途径的激活。阻断 JAK/STAT 途径可能会降低 PVL(+)MRSA 肺炎的严重程度。
