Central Veterinary Institute of Wageningen University and Research Centre, Edelhertweg 15, 8219 PH Lelystad, The Netherlands.
J Dairy Sci. 2013 Jun;96(6):3723-36. doi: 10.3168/jds.2012-6320. Epub 2013 Apr 12.
Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment.
停乳链球菌是一种高度流行的奶牛乳腺炎病原体，给奶业造成了巨大的经济损失。本研究旨在研究实验性攻毒后急性炎症期间的宿主反应。在 3 头奶牛中，比较了受感染和对照乳区中对停乳链球菌反应的基因表达。在 16 个不同位置采集了所有乳区（n=16）的样本。微阵列数据显示，感染和对照乳区之间有 239 个基因差异表达。在不同位置之间未观察到基因表达的差异。使用定量 PCR 分析对微阵列数据进行了几个基因的验证。由于早期停乳链球菌乳腺炎而差异表达的基因代表了感染过程的几个阶段：（1）病原体识别；（2）中性粒细胞的趋化作用；（3）组织修复机制；和（4）杀菌活性。诱导了 3 种不同的病原体识别基因：纤维胶凝蛋白、脂多糖结合蛋白和 Toll 样受体 2。在早期炎症中，钙粒蛋白被发现是上调最明显的基因。通过组织学和免疫组织化学，我们证明了对停乳链球菌的基因表达变化不仅在浸润的乳体细胞中，而且在乳腺上皮细胞中均被诱导，表明后者细胞类型在乳汁生成以及免疫反应中均发挥作用。由于感染后炎症或乳腺炎迅速发展，因此需要早期诊断（停乳链球菌）乳腺炎以预防疾病和病原体传播。宿主反应的深入了解有助于设计免疫调节疗法来减轻（早期）诊断停乳链球菌乳腺炎后的炎症。未来的研究应集中于开发这些早期诊断和乳腺炎治疗的免疫调节成分。
