Vitamin D upregulates the macrophage complement receptor immunoglobulin in innate immunity to microbial pathogens

• Published in: Communications biology Vol. 4; no. 1; p. 401
• Main Authors: Small, Annabelle G., Harvey, Sarah, Kaur, Jaspreet, Putty, Trishni, Quach, Alex, Munawara, Usma, Perveen, Khalida, McPhee, Andrew, Hii, Charles S., Ferrante, Antonio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25-03-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/31; 38; 38/77; 631/250/2499; 631/250/2504/342/1726; 631/443/810; 692/420/254; 82/1; 82/29; 82/80; Agonists; Biology; Biomedical and Life Sciences; Calcitriol; Cell surface; Complement receptors; Immunoglobulins; Innate immunity; Life Sciences; Macrophages; Monocytes; mRNA; Phagocytosis; Toll-like receptors; Vitamin D; Vitamin D3; Vitamin deficiency
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-01943-3

Vitamin D deficiency remains a global concern. This ‘sunshine’ vitamin is converted through a multistep process to active 1,25-dihydroxyvitamin D
3
(1,25D), the final step of which can occur in macrophages. Here we demonstrate a role for vitamin D in innate immunity. The expression of the complement receptor immunoglobulin (CRIg), which plays an important role in innate immunity, is upregulated by 1,25D in human macrophages. Monocytes cultured in 1,25D differentiated into macrophages displaying increased CRIg mRNA, protein and cell surface expression but not in classical complement receptors, CR3 and CR4. This was associated with increases in phagocytosis of complement opsonised
Staphylococcus aureus
and
Candida albicans
. Treating macrophages with 1,25D for 24 h also increases CRIg expression. While treating macrophages with 25-hydroxyvitamin D
3
does not increase CRIg expression, added together with the toll like receptor 2 agonist, triacylated lipopeptide, Pam3CSK4, which promotes the conversion of 25-hydroxyvitamin D
3
to 1,25D, leads to an increase in CRIg expression and increases in CYP27B1 mRNA. These findings suggest that macrophages harbour a vitamin D-primed innate defence mechanism, involving CRIg.
Annabelle Small et al. report a new role for vitamin D in innate immunity. They find that the vitamin D metabolite 1,25D increases phagocytosis and expression of complement receptor immunoglobulin (CRIg) by macrophages and that treatment of macrophages with a toll like receptor 2 agonist promotes conversion of 25-hydroxyvitamin D3 to 1,25D.