AUTHOR=Wherry Taylor L. T. , Mooyottu Shankumar , Stabel Judith R. 

TITLE=Effects of 1,25-Dihydroxyvitamin D3 and 25-Hydroxyvitamin D3 on PBMCs From Dairy Cattle Naturally Infected With Mycobacterium avium subsp. paratuberculosis

JOURNAL=Frontiers in Veterinary Science

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2022.830144

DOI=10.3389/fvets.2022.830144

ISSN=2297-1769

ABSTRACT=<p>The role of vitamin D<sub>3</sub> in modulating immune responses has been well-established for over two decades; however, its specific functions have not been extensively detailed in cattle, particularly cattle in different stages of infection with <italic>Mycobacterium avium</italic> subspecies <italic>paratuberculosis</italic> (MAP). Consistent with previous work in our lab, the present study showed that infected cattle in the clinical stage of disease have reduced serum 25-hydroxyvitamin D<sub>3</sub> [25(OH)D<sub>3</sub>]. Additionally, effects of vitamin D<sub>3</sub> on peripheral blood mononuclear cells (PBMCs) from naturally infected dairy cattle in subclinical (<italic>n</italic> = 8) or clinical (<italic>n</italic> = 8) stages of infection were compared to non-infected control cows (<italic>n</italic> = 8). Briefly, PBMCs were isolated and cultured <italic>in vitro</italic> with 4 ng/ml 1,25-dihydroxyvitamin D<sub>3</sub> [1,25(OH)<sub>2</sub>D<sub>3</sub>] or 100 ng/ml 25(OH)D<sub>3</sub>. Treatment with 1,25(OH)<sub>2</sub>D<sub>3</sub> resulted in decreased secretion for some pro-inflammatory cytokines in clinical animals, including IL-1β, IL-6, and IFN-γ. Similar responses for IL-1β and IL-6 were noted with the addition of 25(OH)D<sub>3</sub>. Additionally, pro-inflammatory cytokine gene expression tended to be upregulated in PBMCs from clinical animals after treatment with 1,25(OH)<sub>2</sub>D<sub>3</sub>. In contrast, PBMCs from clinical animals treated with 25(OH)D<sub>3</sub> showed downregulation of pro-inflammatory cytokine gene expression, although only significant for <italic>IL1B</italic>. Following 25(OH)D<sub>3</sub> treatment, clinical animals showed significant reduction in CD4+CD25+ T cells. <italic>CYP27B1</italic> gene expression was notably decreased in clinical and control animals following 25(OH)D<sub>3</sub> treatment but increased in subclinical cows. 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment reduced <italic>CYP24A1</italic> gene expression in all groups, while 25(OH)D<sub>3</sub> treatment only significantly reduced expression for control cows. Lastly, serum 25(OH)D<sub>3</sub> levels were significantly lower in clinical animals. Taken together, these data show vitamin D<sub>3</sub> modulates cytokine signaling in cattle at different stages of MAP infection and, therefore, may have implications on disease progression.</p>