Toll-like receptor (TLR) 2/1 signalling is linked to autophagy through transcriptional actions of the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-vitamin D receptor (VDR) complex. Population-specific effects have been reported for TLR2/1-VDR signalling. We hypothesized that population effects extend to autophagy and are influenced by vitamin D status. Serum 25(OH)D3 of healthy South Africans (Black individuals n = 10, White individuals n = 10) was quantified by LC-MS/MS. Primary monocytes-macrophages were supplemented in vitro with 1,25(OH)2D3 and stimulated with the lipoprotein Pam3CysSerLys4. TLR2, VDR, hCAP18, Beclin1, LC3-IIB, cytokines and CYP24A1 mRNA were quantified by flow cytometry and RT-qPCR, respectively. Black individuals showed significantly lower overall cumulative LC3-IIB (P < 0.010), but higher Beclin1, VDR, IL6 and TNFA (P < 0.050) than White individuals. 1,25(OH)2D3 enhanced autophagic flux in monocytes-macrophages from Black individuals upon TLR2/1 stimulation and strengthened autophagy in 25(OH)D3 deficient individuals (independent cohort, n = 20). These findings support population-directed vitamin D supplementation.

中文翻译：

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自噬功效和维生素D状态：种群效应。

Toll样受体（TLR）2/1信号通过1,25-二羟基维生素D3（1,25（OH）2D3）-维生素D受体（VDR）复合物的转录作用与自噬相关。已经报道了针对TLR2 / 1-VDR信号的特定人群效应。我们假设人口影响扩展到自噬，并受维生素D状态的影响。通过LC-MS / MS对健康南非人的血清25（OH）D3（黑人个体n = 10，白人个体n = 10）进行定量。在体外向原代单核细胞-巨噬细胞补充1,25（OH）2D3，并用脂蛋白Pam3CysSerLys4刺激。通过流式细胞仪和RT-qPCR分别定量TLR2，VDR，hCAP18，Beclin1，LC3-IIB，细胞因子和CYP24A1 mRNA。黑人个体的总累积LC3-IIB显着较低（P <0.010），但Beclin1，VDR，IL6和TNFA较高（P <0。050）比白人个人。1,25（OH）2D3在TLR2 / 1刺激下增强了黑人个体单核巨噬细胞的自噬通量，并在25（OH）D3缺陷个体（独立队列，n = 20）中增强了自噬。这些发现支持以人群为导向的维生素D补充。