Animal and Bioscience Department, Teagasc, Grange, Dunsany, Co. Meath, Ireland.
School of Veterinary Medicine, University College Dublin, Dublin 4, Ireland.
BMC Genomics. 2021 Nov 5;22(1):796. doi: 10.1186/s12864-021-08135-7.
Mastitis is an economically important disease of dairy cows with Staphylococcus aureus a major cause worldwide. Challenge of Holstein-Friesian cows demonstrated that S. aureus strain MOK124, which belongs to Clonal Complex (CC)151, caused clinical mastitis, while strain MOK023, belonging to CC97, caused mild or subclinical mastitis. The aim of this study was to elucidate the molecular mechanisms of the host immune response utilising a transcriptomic approach. Milk somatic cells were collected from cows infected with either S. aureus MOK023 or MOK124 at 0, 24, 48, 72 and 168 h post-infection (hpi) and analysed for differentially expressed (DE) genes in response to each strain.
In response to MOK023, 1278, 2278, 1986 and 1750 DE genes were found at 24, 48, 72 and 168 hpi, respectively, while 2293, 1979, 1428 and 1544 DE genes were found in response to MOK124 at those time points. Genes involved in milk production (CSN1, CSN10, CSN1S2, CSN2, a-LACTA and PRLR) were downregulated in response to both strains, with a more pronounced decrease in the MOK124 group. Immune response pathways such as NF-κB and TNF signalling were overrepresented in response to both strains at 24 hpi. These immune pathways continued to be overrepresented in the MOK023 group at 48 and 72 hpi, while the Hippo signalling, extracellular matrix interaction (ECM) and tight junction pathways were overrepresented in the MOK124 group between 48 and 168 hpi. Cellular composition analysis demonstrated that a neutrophil response was predominant in response to MOK124, while M1 macrophages were the main milk cell type post-infection in the MOK023 group.
A switch from immune response pathways to pathways involved in maintaining the integrity of the epithelial cell layer was observed in the MOK124 group from 48 hpi, which coincided with the occurrence of clinical signs in the infected animals. The higher proportion of M1 macrophages in the MOK023 group and lack of substantial neutrophil recruitment in response to MOK023 may indicate immune evasion by this strain. The results of this study highlight that the somatic cell transcriptomic response to S. aureus is dependent on the genotype of the infecting strain.
乳腺炎是一种具有重要经济意义的奶牛疾病，金黄色葡萄球菌是全球范围内的主要病因。对荷斯坦-弗里生奶牛的挑战表明，属于克隆群（CC）151 的金黄色葡萄球菌 MOK124 株引起临床乳腺炎，而属于 CC97 的 MOK023 株引起轻度或亚临床乳腺炎。本研究旨在利用转录组学方法阐明宿主免疫反应的分子机制。在感染金黄色葡萄球菌 MOK023 或 MOK124 后 0、24、48、72 和 168 小时，从奶牛的乳体细胞中收集样本，并分析对每种菌株的差异表达（DE）基因。
MOK023 组在 24、48、72 和 168 小时时分别发现了 1278、2278、1986 和 1750 个 DE 基因，而 MOK124 组在这些时间点时分别发现了 2293、1979、1428 和 1544 个 DE 基因。与两种菌株反应时，与乳蛋白合成相关的基因（CSN1、CSN10、CSN1S2、CSN2、a-LACTA 和 PRLR）下调，其中 MOK124 组下调更明显。NF-κB 和 TNF 信号等免疫途径在 24 小时时对两种菌株均呈过度表达，而 Hippo 信号、细胞外基质相互作用（ECM）和紧密连接途径在 MOK023 组在 48 和 72 小时时过度表达，而在 MOK124 组在 48 至 168 小时时，这些途径过度表达。细胞组成分析表明，对 MOK124 的反应主要是中性粒细胞反应，而 M1 巨噬细胞是 MOK023 组感染后乳细胞的主要类型。
从 48 小时开始，MOK124 组的免疫反应途径从细胞层完整性维持途径转换，这与感染动物临床症状的发生相吻合。在 MOK023 组中 M1 巨噬细胞的比例较高，而对 MOK023 的中性粒细胞募集量没有显著增加，这可能表明该菌株的免疫逃避。本研究的结果表明，金黄色葡萄球菌引起的体细胞转录组反应取决于感染菌株的基因型。
