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Staphylococcus aureus  ( S. aureus ) is problematic for lactating mammals and public health. Understanding of mechanisms by which the hosts respond to severe invasion of  S. aureus  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  S. aureus . Compared to the negative control quarters, 194 highly-confident responsive genes were identified in the quarters with high concentration (10 9  cfu/mL) of  S. aureus , 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 6  cfu/mL) of  S. aureus , 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  S. aureus . Network analysis suggested that the two miRNAs' pivotal roles in defending hosts against bacterial infection probably through inhibiting  CXCL14  and  KIT . The significant down-regulation of  CXCL14  was also observed in bovine mammary epithelial cells at 24 h post-infection of  S. aureus  (10 8  cfu/mL)  in vitro . Integrated analysis with QTL database further suggested 28 genes (e.g.,  CXCL14, KIT , and  SLC4A11 ) as candidates of bovine mastitis. This study first systematically revealed transcriptional and post-transcriptional responses of bovine mammary gland cells to invading  S. aureus  in a dosage-dependent pattern, and highlighted a complicated responsive mechanism in a network of miRNA-gene-pathway interplay.

frontiers in cellular and infection microbiology

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