Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae.
BACKGROUND
Streptococcus pneumoniae forms part of the normal nasopharyngeal flora but can also cause a broad spectrum of inflammatory diseases. Vitamin D has potent effects on human immunity, including induction of antimicrobial peptides and suppression of T-cell proliferation, but its ability to modulate the immune response to pneumococci is unknown.


METHODS
Monocyte-derived dendritic cells (DCs) were stimulated with pneumococcal peptidoglycan (PGN) in the presence or absence of vitamin D. Expression of maturation markers, cytokines, pattern recognition receptors, and antimicrobial peptides were measured with flow cytometry, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Stimulated DCs were cocultured with autologous T-helper cells, and concentrations of T-helper (Th) 1-, Th17-, and regulatory T-cell-related cytokines were measured with enzyme-linked immunosorbent assay.


RESULTS
Vitamin D enhanced DC maturation and expression of the migration marker C-C chemokine receptor type 7 (CCR7) in PGN-stimulated cells. It also enhanced expression of key pattern recognition receptors (Toll-like receptor 2, Nucleotide-binding oligomerization domain-containing protein 2 [Nod2]) and induced a synergistic up-regulation of the inflammatory mediator IL-1β and the β-defensin Human Beta Defensin 3 (hBD-3). Furthermore, vitamin D skewed the DC-mediated T-helper response to PGN from an inflammatory Th1/Th17 phenotype toward a regulatory T-cell phenotype.


CONCLUSIONS
Vitamin D modulates key elements of innate immunity while dampening adaptive immune responses in DCs after pneumococcal challenge, which may have implications for prevention and treatment of pneumococcus-induced inflammation.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Marie
M
Olliver
Laura
L
Spelmink
Jeffni
J
Hiew
Ulf
U
Meyer-Hoffert
Birgitta
B
Henriques-Normark
Peter
P
Bergman
D056704:Adaptive Immunity / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015638:Cytochalasin D / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007155:Immunologic Factors / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010457:Peptidoglycan / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology; D058504:Th17 Cells / Q000276:immunology / Q000382:microbiology; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology*; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D016207:Cytokines; C422950:DEFB103A protein, human; D007155:Immunologic Factors; D010457:Peptidoglycan; D051193:Toll-Like Receptors; D023083:beta-Defensins; D014807:Vitamin D; D015638:Cytochalasin D
Streptococcus pneumoniae; Vitamin D; antimicrobial peptides; dendritic cell; immune modulation