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

• Published in: Scientific reports 2023-07, Vol.13 (1), p.10846-10846, Article 10846
• Main Authors: Reid, Cian, Flores-Villalva, Susana, Remot, Aude, Kennedy, Emer, O’Farrelly, Cliona, Meade, Kieran G.
• Format: Article
• Language: English
• Subjects: 631/250/262; 631/250/98; Animal biology; Blood cells; Chemokines; CX3CR1 protein; Enzyme-linked immunosorbent assay; Feed additives; Gene expression; Humanities and Social Sciences; Immune response; Immunology; Inflammasomes; Innate immunity; Interleukin 1; Interleukin 8; Life Sciences; Ligands; Lipopolysaccharides; multidisciplinary; Science; Science (multidisciplinary); Stat1 protein; Transcriptomics; Vitamin D; Vitamin D3; Vitamin deficiency
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-37427-z

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.