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This \u2018sunshine\u2019 vitamin is converted through a multistep process to active 1,25-dihydroxyvitamin D<jats:sub>3<\/jats:sub> (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 <jats:italic>Staphylococcus aureus<\/jats:italic> and <jats:italic>Candida albicans<\/jats:italic>. Treating macrophages with 1,25D for 24\u2009h also increases CRIg expression. While treating macrophages with 25-hydroxyvitamin D<jats:sub>3<\/jats:sub> 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<jats:sub>3<\/jats:sub> 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.<\/jats:p>","DOI":"10.1038\/s42003-021-01943-3","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T11:06:58Z","timestamp":1616670418000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Vitamin D upregulates the macrophage complement receptor immunoglobulin in innate immunity to microbial pathogens"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6275-2847","authenticated-orcid":false,"given":"Annabelle G.","family":"Small","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaspreet","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trishni","family":"Putty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-7581","authenticated-orcid":false,"given":"Alex","family":"Quach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usma","family":"Munawara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1499-1736","authenticated-orcid":false,"given":"Khalida","family":"Perveen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"McPhee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles S.","family":"Hii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2581-6407","authenticated-orcid":false,"given":"Antonio","family":"Ferrante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"1943_CR1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.chembiol.2013.12.016","volume":"21","author":"DD Bikle","year":"2014","unstructured":"Bikle, D. 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