Whole transcriptome analysis of Mycoplasma bovis-host interactions under in vitro and in vivo conditions

Mycoplasma bovis mastitis is becoming increasingly problematic for dairy cattle farming. M. bovis is inherently resistant to beta-lactam antimicrobials and no effective vaccine is available. The major constraints to developing effective control tools are limited knowledge of M. bovis virulence factors and the underlying pathogenic mechanisms. The objective of this study was to determine virulence-associated genes of M. bovis and host immune response genes expressed during the early stages of host-pathogen interactions. We conducted in vitro infection of mammary epithelial cell (MAC-T) lines and in vivo intramammary infection of dairy cows with M. bovis strain PG45 and evaluated whole transcriptome differential gene expression. A total of 614 and 7161 genes of M. bovis and bovine host cells were differentially expressed, respectively. Insertion sequence (IS) genes that are involved in transposase activity such as ISMbov1, ISMbov2, ISMbov3, and ISMbov9 were significantly upregulated, whereas protein translation-associated genes were significantly downregulated. In MAC-T cells, genes involved in apoptosis pathways and proinflammatory cytokines were significantly upregulated, whereas genes involved in cell cycle, ribosome biogenesis, and steroid biosynthesis were significantly downregulated. Genes encoding formation of neutrophil extracellular traps and proinflammatory cytokines, were significantly upregulated in the mammary gland of M. bovis challenged cows, whereas genes involved in steroid biosynthesis and metabolism were significantly downregulated. Altogether, while our findings shed light on the simultaneous transcriptional changes in M. bovis and the host during infection, further studies are required to understand a complete picture of these interactions that lead to mastitis.