State key Laboratory of Agricultural Microbiology, Division of Animal Infectious Disease, Huazhong Agricultural University, Wuhan, Hubei, China.
BMC Genomics. 2012 Feb 13;13:68. doi: 10.1186/1471-2164-13-68.
Haemophilus parasuis (H. parasuis) is the etiological agent of Glässer's disease in pigs. Currently, the molecular basis of this infection is largely unknown. The innate immune response is the first line of defense against the infectious disease. Systematical analysis on host innate immune response to the infection is important for understanding the pathogenesis of the infectious microorganisms.
A total of 428 differentially expressed (DE) genes were identified in the porcine alveolar macrophages (PAMs) 6 days after H. parasuis infection. These genes were principally related to inflammatory response, immune response, microtubule polymerization, regulation of transcript and signal transduction. Through the pathway analysis, the significant pathways mainly concerned with cell adhesion molecules, cytokine-cytokine receptor interaction, complement and coagulation cascades, toll-like receptor signaling pathway, MAPK signaling pathway, suggesting that the host took different strategies to activate immune and inflammatory response upon H. parasuis infection. The global interactions network and two subnetworks of the proteins encoded by DE genes were analyzed by using STRING. Further immunostimulation analysis indicated that mRNA levels of S100 calcium-binding protein A4 (S100A4) and S100 calcium-binding protein A6 (S100A6) in porcine PK-15 cells increased within 48 h and were sustained after administration of lipopolysaccharide (LPS) and Poly (I:C) respectively. The s100a4 and s100a6 genes were found to be up-regulated significantly in lungs, spleen and lymph nodes in H. parasuis infected pigs. We firstly cloned and sequenced the porcine coronin1a gene. Phylogenetic analysis showed that poCORONIN 1A belonged to the group containing the Bos taurus sequence. Structural analysis indicated that the poCORONIN 1A contained putative domains of Trp-Asp (WD) repeats signature, Trp-Asp (WD) repeats profile and Trp-Asp (WD) repeats circular profile at the N-terminus.
Our present study is the first one focusing on the response of porcine alveolar macrophages to H. parasuis. Our data demonstrate a series of genes are activated upon H. parasuis infection. The observed gene expression profile could help screening the potential host agents for reducing the prevalence of H. parasuis and further understanding the molecular pathogenesis associated with H. parasuis infection in pigs.
副猪嗜血杆菌(H. parasuis)是引起猪格拉泽氏病的病原体。目前,这种感染的分子基础在很大程度上尚不清楚。先天免疫反应是抵御传染病的第一道防线。系统分析宿主对感染的先天免疫反应对于了解传染病微生物的发病机制非常重要。
在副猪嗜血杆菌感染后 6 天,猪肺泡巨噬细胞(PAMs)中鉴定出 428 个差异表达(DE)基因。这些基因主要与炎症反应、免疫反应、微管聚合、转录调控和信号转导有关。通过通路分析,显著通路主要与细胞黏附分子、细胞因子-细胞因子受体相互作用、补体和凝血级联、Toll 样受体信号通路、MAPK 信号通路有关,表明宿主在副猪嗜血杆菌感染时采取了不同的策略来激活免疫和炎症反应。通过 STRING 分析了 DE 基因编码蛋白的全局相互作用网络和两个子网。进一步的免疫刺激分析表明,猪 PK-15 细胞中 S100 钙结合蛋白 A4(S100A4)和 S100 钙结合蛋白 A6(S100A6)的 mRNA 水平在脂多糖(LPS)和 Poly(I:C)给药后 48 小时内增加,并持续升高。在副猪嗜血杆菌感染的猪中,s100a4 和 s100a6 基因在肺部、脾脏和淋巴结中显著上调。我们首次克隆和测序了猪 coronin1a 基因。系统进化分析表明,poCORONIN 1A 属于包含牛序列的组。结构分析表明,poCORONIN 1A 在 N 端含有假定的 Trp-Asp(WD)重复特征、Trp-Asp(WD)重复图谱和 Trp-Asp(WD)重复圆形图谱结构域。
本研究首次关注了猪肺泡巨噬细胞对副猪嗜血杆菌的反应。我们的数据表明,在副猪嗜血杆菌感染后,一系列基因被激活。观察到的基因表达谱有助于筛选潜在的宿主因子,以降低副猪嗜血杆菌的流行率,并进一步了解与副猪嗜血杆菌感染相关的分子发病机制。