title: Species-specific regulation of innate immunity by vitamin D signaling.
abstract: While many global mechanisms of innate immune responses to pathogen threat are conserved over a vast range of species, the details of those responses and their regulation appear to be highly species-specific. An array of studies over recent years has revealed that hormonal vitamin D is an important regulator of innate immunity. In humans, the hormone-bound VDR directly induces the transcription of genes encoding antimicrobial peptides (AMPs), pattern recognition receptors and key cytokines implicated in innate immune responses. We find that the vitamin D response elements (VDREs) in a number of these human genes are highly conserved in a range of primates, but not present in rodent genes. Consistent with this, VDR target genes encoding AMPs human beta-defensin 2 (HBD2) and cathelicidin (CAMP) and the pattern recognition receptor NOD2 are induced by 1,25(OH)2D in human cells of epithelial or myeloid origin but not similarly regulated in mouse cells. In addition, while conditioned media from human epithelial cells treated with 1,25(OH)2D produced antimicrobial activity against E. coli and the lung pathogen Pseudomonas aeruginosa, no such activity was detected in conditioned media from comparable 1,25(OH)2D-treated mouse epithelial cells. Given that other work has provided evidence that 1,25(OH)2D does control innate immune responses in mouse models of disease, we discuss the species-specific similarities and differences in 1,25(OH)2D-regulated innate immunity.
authors.affiliation: Departments of Physiology and Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Vassil
authors.initials: V
authors.lastname: Dimitrov
authors.affiliation: Departments of Physiology and Medicine, McGill University, Montreal, Quebec, Canada. Electronic address: john.white@mcgill.ca.
authors.forename: John H
authors.initials: JH
authors.lastname: White
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001483:Base Sequence; D054804:Cathelicidins / Q000235:genetics* / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D061251:Primary Cell Culture; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D015398:Signal Transduction; D013045:Species Specificity; D014807:Vitamin D / Q000494:pharmacology*; D030181:Vitamin D Response Element; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics* / Q000276:immunology; D023083:beta-Defensins / Q000235:genetics* / Q000276:immunology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D017077:Culture Media, Conditioned; C106641:DEFB4A protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D023083:beta-Defensins; D014807:Vitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase
keywords: Antimicrobial peptides; Innate immunity; Species specificity; VDR target genes; Vitamin D