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

Abstract

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 (109 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 (106 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 (108 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.

Comparison of microRNA Profiles between Bovine Mammary Glands Infected with Staphylococcus aureus and Escherichia coli

“…In the present study, the putative target genes of DIE-miRNAs were annotated as being involved in various classes of immune signalling pathways, TLR signalling pathway, TGF-β signalling pathway, cytokine-cytokine receptor interaction, MAPK signalling pathway, cell adhesion molecules, leukocyte trans endothelial migration, and chemokine signalling pathways. It has been previously reported that these signalling pathways described above are likely associated with the development of mastitis 3 , 49 - 51 . The functions of the putative targets and the corresponding miRNAs' role in the regulation of mammary inflammation indicate that the DIE-miRNAs may play multiple roles in immunity related gene regulation networks.…”

Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitis

“…observed that bta‐mir‐223 and bta‐mir‐21‐3p are significantly upregulated in the quarters infected by high concentration of S. aureus . These miRNAs regulate the expression of immune‐related genes including CXCL14 and KIT , which suggested that miRNAs play a role in mammary gland post‐transcriptional responses of S. aureus ‐induced mastitis . The cell components of milk were largely removed from our milk samples; however, the somatic cells present in milk, including 75% white blood cells and 25% epithelial cells, are increased during mastitis .…”

“…al. observed that bta‐mir‐223 and bta‐mir‐21‐3p are significantly upregulated in the quarters infected by high concentration of S. aureus . These miRNAs regulate the expression of immune‐related genes including CXCL14 and KIT , which suggested that miRNAs play a role in mammary gland post‐transcriptional responses of S. aureus ‐induced mastitis .…”

miRNAs reshape immunity and inflammatory responses in bacterial infection

“…The increase in bta-miR-223 and bta-miR-21-3p was found in the teat quarters following high dose S. aureus infection. Further analysis suggested critical roles of these two miRNAs in defending hosts against bacterial infection, probably through inhibiting CXCL14 and KIT proto-oncogene receptor tyrosine kinase (KIT) 90 . Skin wound healing after S. aureus infection might be impaired in miR-142-deficient mice compared to that in wild-type mice.…”