Abstract
Vitamin D (VitD) is an endogenous immunomodulator that could protect from HIV-1 infection reducing immune activation and inducing the expression of anti-HIV-1 peptides. To establish a correlation between VitD and natural resistance to HIV-1 infection, a case-control study using blood and mucosa samples of 58 HIV-1-exposed but seronegative (HESN) individuals, 43 HIV-1 seropositives (SPs) and 59 non-exposed healthy controls (HCs) was carried out. The VitD concentration in plasma was determined by ELISA, and mRNA relative units (RU) of VDR, IL-10, TGF-β, TNF-α and IL-1β in peripheral blood mononuclear cells (PBMCs), oral and genital mucosa was quantified by qRT-PCR. mRNA levels of human beta-defensin (HBD) -2 and -3 were previously reported and used for correlations. Significantly higher levels of VitD were found in plasma as well as higher mRNA RU of VDR in PBMCs, and in genital mucosa from HESN compared to HCs. In addition, higher mRNA RU of TNF-α, IL-1β and IL-10, and lower mRNA RU of TGF-β were found in PBMC from HESNs compared to HCs. We also observed higher IL-10 mRNA RU in genital mucosa of HESNs compared to HCs, and the mRNA levels of TNF-α in oral and genital mucosa of SPs were higher compared to HESNs. Furthermore, positive correlations between VDR and IL-10 mRNA RU in PBMCs and genital mucosa of HESNs were found. Finally, HBD-2 and HBD-3 mRNA RU were positively correlated with VDR mRNA expression in oral mucosa from HESNs. These results suggest that high levels of VitD and its receptor are associated with natural resistance to HIV-1 infection. Up-regulation of the anti-inflammatory IL-10, and the induction of anti-HIV-1 defensins in mucosa might be part of the mechanisms involved in this association. However, further studies are required to define causal associations.
Highlights
Several mechanisms of protection against HIV-1 infection have been reported in HIV-1 highly exposed, but seronegative (HESN) individuals (Reviewed in 1); they do not explain the absence of infection in all HESNs
Higher VDR mRNA relative units (RU) were observed in vaginal mucosa of HESNs compared to healthy controls (HCs)
Higher levels of IL-10 transcripts in vaginal mucosa of HESNs compared to HCs
Summary
Several mechanisms of protection against HIV-1 infection have been reported in HIV-1 highly exposed, but seronegative (HESN) individuals (Reviewed in 1); they do not explain the absence of infection in all HESNs. further studies are required to fully understand the phenomenon of HIV-1 natural resistance to define new therapeutic targets. Along with its receptor (VDR), they induce transcription of antimicrobial peptides [4] such as human beta defensins (HBD) that possess anti-HIV-1 activity in vitro [5], and play a potential protective role during exposure to HIV-1 in oral mucosa of the Colombian HESN population [6], (Zapata et al, 2012, submitted for publication). VitD might reduce the immune activation and the number of viral target cells [2,3,7], further supporting its beneficial role in natural resistance to HIV-1 infection. Genetic variants related to high VitD and VDR function have been associated with susceptibility to HIV-1 infection [10], suggesting a potential pathogenic role of the VitD/VDR axis
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