MicroRNA profiling in bovine serum according to the stage of Mycobacterium avium subsp. paratuberculosis infection

Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease (JD), and it causes diarrhea and weakness in cattle. During a long subclinical stage, infected animals without clinical signs shed pathogens through feces. For this reason, the diagnosis of JD during the subclinical stage is very important. Circulating miRNAs are attracting attention as useful biomarkers in various veterinary diseases because of their expression changes depending on the state of the disease. Based on current knowledge, circulating miRNAs extracted from bovine serum were used to develop a diagnostic tool for JD. In this study, the animals were divided into 4 groups according to fecal shedding, the presence of antibodies, and clinical signs. Gene expression was analyzed by performing miRNA sequencing for each group, and it was identified that the miRNA expression changed more as the MAP infection progressed. The eight miRNAs that were differentially expressed in all infected groups were selected as biomarker candidates based on their significant differences compared to the control group. These biomarker candidates were validated by qRT-PCR. Considering the sequencing data, two upregulated miRNAs and two downregulated miRNAs showed the same trend in the validation results. Network analysis was also conducted and the results showed that mRNAs (IL-10, TGF-β1) associated with regulatory T cells were predicted to be activated in the subclinical stage. Taken together, our data suggest that two miRNAs (bta-miR-374b, bta-miR-2887) may play major roles in the immune response to MAP infection during the subclinical stage.

MicroRNAs modulate immunological and inflammatory responses in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis

“…Similarly, Shaughnessy et al did not detect differentially expressed miRNAs at either the early 6 months or late (43, 46, and 49 months) intervals across seropositive and seronegative animals 34 . Using naturally infected cattle previous studies compared the miRNA profiles of cattle positive and negative for MAP antibodies by ELISA 32 or compared miRNA profiles according to the stage of MAP infection defined by fecal shedding, ELISA, and clinical signs 53 . In cattle, however, signs of infection such as the appearance of focal lesions in gut tissues can be detected before fecal shedding and ELISA, and therefore, examining the transcriptome of animals according to the histopathological lesions facilitates the identification of animals in the subclinical stage of the infection when the amount of MAP and antibodies can be undetected with current pre-mortem diagnostic methods.…”

Exploring the miRNAs Profile in Dark-Cutting Beef

“…miR-27a-5p acts as a negative regulator of adipocyte differentiation and lipid metabolism and a positive regulator of cell proliferation [ 57 ]. miR-2887 is involved in the regulation of immune and inflammatory responses [ 58 ]. Also, miR-11987 and miR-11972 have been shown to be involved in the autophagic process by negatively regulating their target genes, RAC3 and CLN7 [ 58 , 59 ].…”

“…miR-2887 is involved in the regulation of immune and inflammatory responses [ 58 ]. Also, miR-11987 and miR-11972 have been shown to be involved in the autophagic process by negatively regulating their target genes, RAC3 and CLN7 [ 58 , 59 ]. RAC3 is a negative regulator of autophagy; therefore, its downregulation by miR-11972 could promote autophagy in DFD beef.…”

Association of plasma miRNAs with early life performance and aging in dairy cattle

“…In cattle, miR-363 was upregulated during Mycobacterium avium subsp. paratuberculosis infection [ 54 ]. We found that this miRNA was elevated in spleen and lymph node, consistent with a role in inflammation.…”