1,25-dihydroxyvitamin D3 Modulates Cytokine Production Induced by Candida albicans: Impact of Seasonal Variation of Immune Responses

Abstract

Background. Our interest in immunological effects produced by vitamin D 3 (1,25(OH) 2 D 3 ) and its therapeutic potential prompted us to examine the role of 1,25(OH) 2 D 3 on cytokine production by Candida albicans.Methods. Peripheral blood mononuclear cells (PBMC) with stimulated C. albicans and 1,25(OH) 2 D 3 , cytokine concentrations were measured in supernatant. Quantitative polymerase chain reaction (qPCR) was performed for T cell transcription factors, SOCS1 and 3. TLR2/4, Dectin-1, and mannose receptor expression was studied using flow cytometry and qPCR. An ex-vivo stimulation study was carried out in healthy volunteers to investigate the seasonality of immune response to C. albicans.Results. Upon in vitro C. albicans stimulation, 1,25(OH) 2 D 3 induced a dose-dependent, down-regulation of IL-6, TNFa, IL-17, and IFNc. It also increased IL-10 production. The shift in cytokine profile was not due to 1,25(OH) 2 D 3 augmenting expression of either Thelper differentiation factors or SOCS1 and SOCS3 mRNA. 1,25(OH) 2 D 3 inhibited TLR2, TLR4, Dectin-1, and MR mRNA and protein expression. In our seasonality study, both IL-17 and IFNc levels were suppressed in summer when 25(OH)D 3 levels were elevated.Conclusion. Vitamin D 3 skews cytokine responses toward an antiinflammatory profile, mediated by suppression of TLR2, TLR4, Dectin-1, and MR transcription, leading to reduced surface expression. The biological relevance of these effects has been confirmed by the seasonality of cytokine responses.

Vitamin D Insufficiency among Women Post-Partum in Northern Sweden—A Public Health Concern

“…From the longitudinal data by Lundqvist et al [14] it can be assumed that mothers in the present study who were insufficient post-partum may also have been insufficient during pregnancy. Although the confidence interval of the estimate was wide, resulting in uncertainty, these findings could be consistent with studies reporting vitamin D insufficiency to be associated with susceptibility to a variety of infections as for example respiratory tract infections and candidemia [5] [21] and that vitamin D modulates the immune response to Candida [2]. Cut-off levels for vitamin D were originally set in relation to the role of vitamin D in bone mineralization, with levels <25 nmol/L (10 ng/mL) often referred to vitamin D deficiency and <50 nmol/L (20 ng/mL) as vitamin D insufficiency [11], both associated with decreased bone mineralization and increased fracture risk.…”

“…The association between vitamin D levels and chronic and infectious diseases has elicited an increasing scientific interest. Vitamin D modulates immune function influencing different cell types and it has been shown that vitamin D modify proinflammatory cytokine responses [2] [3] [4]. Further, patients with candidemia had lower levels of vitamin D [5].…”

Hubungan Kadar 25-Hidroksi-Vitamin D dengan HbA1c Melalui Interleukin-17 pada Anak Diabetes Melitus Tipe 1

“…Penelitian sebelumnya melaporkan bahwa vitamin D3 (1,25(OH)2D3) mempunyai kemampuan meng hambat produksi (downregulation) IL-17A dan be berapa sitokin lain. 29 Pada kasus reumatoid artritis, sklerosis multipel, dan kolitis tahap awal. 30 Mekanisme hambatan produksi IL-17A ada pada tingkat nuclear factor for activated T cells (NFAT).…”

“…Hasil ter sebut tidak sesuai dengan penelitian sebelum nya yang melaporkan korelasi postif antara ekspresi dan aktivitas Th17 dengan kontrol glikemik. Penelitian sebelumnya melaporkan bahwa terdapat up-regulation sel Th17 dan defek fungsional sel Treg pada kelenjar limfe pankreas pada pasien DMT1 29,35 dan peningkat an aktivitas sel ini menyebabkan eksaserbasi klinis DMT 1, lesi insulitik, dan peningkatan ekspresi IL-17 pankreas. 11,12 HbA1c merupakan penunjuk dari rerata kadar glukosa plasma dan digunakan sebagai marker kontrol glikemik.…”

The Ground State of Innate Immune Responsiveness Is Determined at the Interface of Genetic, Epigenetic, and Environmental Influences

“…The expression of CLEC4E on monocytes altered their responsiveness to Candida albicans; CLEC4E + monocytes were less effective at phagocytosis and clearance, but they produced a stronger cytokine response to Candida challenge. Although relatively little has been reported on the seasonality of mucosal or systemic Candida infections (70,71), CLEC4E is also a key component of host responses to M. tuberculosis, which does have a well-documented seasonality (72,73).…”