AUTHOR=Fang Lingzhao , Hou Yali , An Jing , Li Bingjie , Song Minyan , Wang Xiao , Sørensen Peter , Dong Yichun , Liu Chao , Wang Yachun , Zhu Huabin , Zhang Shengli , Yu Ying 

TITLE=Genome-Wide Transcriptional and Post-transcriptional Regulation of Innate Immune and Defense Responses of Bovine Mammary Gland to Staphylococcus aureus

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=6

YEAR=2016

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2016.00193

DOI=10.3389/fcimb.2016.00193

ISSN=2235-2988

ABSTRACT=<p><italic>Staphylococcus aureus</italic> (<italic>S. aureus</italic>) is problematic for lactating mammals and public health. Understanding of mechanisms by which the hosts respond to severe invasion of <italic>S. aureus</italic> remains elusive. In this study, the genome-wide expression of mRNAs and miRNAs in bovine mammary gland cells were interrogated at 24 h after intra-mammary infection (IMI) with high or low concentrations of <italic>S. aureus</italic>. Compared to the negative control quarters, 194 highly-confident responsive genes were identified in the quarters with high concentration (10<sup>9</sup> cfu/mL) of <italic>S. aureus</italic>, which were predominantly implicated in pathways and biological processes pertaining to innate immune system, such as cytokine-cytokine receptor interaction and inflammatory response. In contrast, only 21 highly-confident genes were significantly differentially expressed in face of low concentration (10<sup>6</sup> cfu/mL) of <italic>S. aureus</italic>, which slightly perturbed the cell signaling and invoked corresponding responses like vasoconstriction, indicating limited perturbations and immunological evading. Additionally, the significant up-regulations of bta-mir-223 and bta-mir-21-3p were observed in the quarters infected by high concentration of <italic>S. aureus</italic>. Network analysis suggested that the two miRNAs' pivotal roles in defending hosts against bacterial infection probably through inhibiting <italic>CXCL14</italic> and <italic>KIT</italic>. The significant down-regulation of <italic>CXCL14</italic> was also observed in bovine mammary epithelial cells at 24 h post-infection of <italic>S. aureus</italic> (10<sup>8</sup> cfu/mL) <italic>in vitro</italic>. Integrated analysis with QTL database further suggested 28 genes (e.g., <italic>CXCL14, KIT</italic>, and <italic>SLC4A11</italic>) as candidates of bovine mastitis. This study first systematically revealed transcriptional and post-transcriptional responses of bovine mammary gland cells to invading <italic>S. aureus</italic> in a dosage-dependent pattern, and highlighted a complicated responsive mechanism in a network of miRNA-gene-pathway interplay.</p>