College of Veterinary Medicine, Jilin University, Changchun, PR China.
Section of Paediatric Infectious Disease, Imperial College London, London, UK.
Vet Microbiol. 2020 Aug;247:108755. doi: 10.1016/j.vetmic.2020.108755. Epub 2020 Jun 12.
Excessive cytokine production is an important component of the acute respiratory distress syndrome and multiple organ failure. Pneumonia can lead to an overexpression of cytokines, although comparatively little is known about the relevance and differences in cytokines between blood and lung. In this study, piglets were experimentally infected intranasally with Actinobacillus pleuropneumoniae (APP), and transcriptomes of lung tissue and peripheral blood mononuclear cells determined. In addition, the levels of 30 cytokines in broncheoalveolar lavage fluid (BALF) and sera were determined by ELISA. Post infection, there was an early increase in lung monocytes, and a later rise in inflammatory cytokines in BALF. Blood lymphocytes increased early in infection and there was a rise in inflammatory cytokines in the peripheral blood of infected piglets. Genes involved in cytokine production, leukocyte migration and differentiation, lymphocyte activation, and cytokine-mediated signaling pathways in the transcriptomes of lung tissue were significantly down-regulated early in infection. At this early phase of APP infection (0-6 h), the cytokines IL-1β, MCP-1, and IL-5 in sera increased rapidly and significantly, while many cytokines in BALF decreased. At 48 h post-infection, cytokines in sera were no longer significantly increased, although some were up-regulated in BALF, and there was aggravated pathological damage in the lungs at this time. The data indicate there are substantial differences between immune cells and cytokines in the lung and peripheral blood of APP infected piglets at equivalent time points. The results increase our understanding of pig-APP host interactive biology, and will be important in formulating future therapeutic and preventative strategies to prevent disease caused by APP.
细胞因子过度产生是急性呼吸窘迫综合征和多器官衰竭的一个重要组成部分。肺炎可导致细胞因子过度表达，尽管关于血液和肺部细胞因子的相关性和差异知之甚少。在这项研究中，猪通过鼻腔内接种胸膜肺炎放线杆菌（APP）进行实验性感染，并确定肺组织和外周血单个核细胞的转录组。此外，通过 ELISA 测定支气管肺泡灌洗液（BALF）和血清中 30 种细胞因子的水平。感染后，肺单核细胞早期增加，BALF 中的炎症细胞因子后期升高。感染猪的血液淋巴细胞早期增加，外周血中的炎症细胞因子升高。肺组织转录组中与细胞因子产生、白细胞迁移和分化、淋巴细胞激活以及细胞因子介导的信号通路相关的基因在感染早期显著下调。在 APP 感染的早期阶段（0-6 小时），血清中 IL-1β、MCP-1 和 IL-5 迅速且显著增加，而 BALF 中的许多细胞因子减少。感染后 48 小时，血清中的细胞因子不再显著增加，尽管 BALF 中的一些细胞因子上调，此时肺部的病理损伤加剧。这些数据表明，在等量时间点，APP 感染猪的肺和外周血中的免疫细胞和细胞因子之间存在很大差异。研究结果增加了我们对猪 APP 宿主相互作用生物学的理解，这对于制定未来预防和治疗 APP 引起的疾病的策略将非常重要。
