Vitamin D signaling in the bovine immune system: a model for understanding human vitamin D requirements.
The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. cdnelson3@wisc.edu
Corwin D
CD
Nelson
Timothy A
TA
Reinhardt
John D
JD
Lippolis
Randy E
RE
Sacco
Brian J
BJ
Nonnecke
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D002417:Cattle; D018946:Chemokine CCL5 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D008414:Mastitis, Bovine / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D018946:Chemokine CCL5; D016207:Cytokines; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D013250:Steroid Hydroxylases; D052247:Nitric Oxide Synthase Type II; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase