Long-term in vivo vitamin D3 supplementation modulates bovine IL-1 and chemokine responses

Abstract

Vitamin D deficiency at birth, followed by prolonged insufficiency in early life may predispose bovine calves to infection and disease. However, the effects of vitamin D levels on innate immunity are unclear due to the lack of long-term supplementation trials in vivo and reliable approaches for reproducibly assessing immune function. Here, a standardized whole blood immunophenotyping assay was used to compare innate immune responses to infection relevant ligands (LPS, Pam3CSK4 and R848) between Holstein–Friesian calves supplemented with vitamin D (n = 12) from birth until 7 months of age and control calves (n = 10) raised on an industry standard diet. Transcriptomic analysis in unstimulated whole blood cells revealed increased expression of type I interferons and chemokines in vitamin D supplemented calves, while IL-1 and inflammasome gene expression was decreased. In response to stimulation with the bacterial ligand LPS, supplemented calves had significantly increased expression of CASP1, CX3CR1, CAT, whereas STAT1 was decreased. Stimulation with the bacterial ligand Pam3CSK4 revealed increased expression of IL1A, IL1B and CAT genes; and decreased C5AR1 expression. In response to the viral ligand R848, STAT1 and S100A8 expression was significantly decreased. An increased IL-1 and inflammasome gene expression signature in vitamin D supplemented calves in response to LPS and Pam3CSK4 was also found, with ELISA confirming increased IL-1β protein production. In contrast, a decreased chemokine gene expression signature was found in response to R848 in supplemented animals, with decreased IL-8 protein expression exhibited in response to all PAMPs also found. These results demonstrated expression of several cytokine, chemokine and inflammasome genes were impacted by vitamin D supplementation in the first 7 months of life, with IL-8 expression particularly responsive to vitamin D. Overall, vitamin D supplementation induced differential innate immune responses of blood immune cells that could have important implications for disease susceptibility in cattle.

Enhancing bovine immune, antioxidant and anti-inflammatory responses with vitamins, rumen-protected amino acids, and trace minerals to prevent periparturient mastitis

“…Furthermore, vitamin D treatment has been associated with increased cell viability and the inhibition of S. aureus adhesion and invasion in bovine mammary epithelial cells, underscoring its potential significance in mastitis prevention ( 202 ). Consistently, a recent published article has demonstrated that vitamin D and its metabolites hydroxyvitamin D [25(OH)D] with a concentration of 20-400 ng/ml has shown a positive role on bovine immune cells, antioxidant response and could be consider as therapeutic agent for mastitis prevention ( 203 – 205 ).In light of the available literature, it is evident that vitamin D holds a central position in bolstering dairy cattle immunity and potentially alleviating bovine mastitis. However, it is worth noting that further comprehensive investigations are warranted to gain a deeper understanding of its precise mechanisms and potential therapeutic applications in this context.…”