Vitamin D Status Modulates Inflammatory Response in HIV+ Subjects: Evidence for Involvement of Autophagy and TG2 Expression in PBMC.

Monica Currò,Daniela Caccamo,Nadia Ferlazzo,Riccardo Ientile,Giovanni Francesco Pellicanò,Flavia D’Andrea,Giuseppe Nunnari,Maria Giovanna Costanzo,Giuseppa Visalli

doi:10.3390/ijms21207558

Monica Currò, Daniela Caccamo + Show 7 more

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https://doi.org/10.3390/ijms21207558

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Abstract

Conflicting results on the involvement of vitamin D deficiency in inflammatory and immune response in HIV+ subjects are reported. We aimed to characterize the possible influence of vitamin D status on changes in expression of tissue transglutaminase gene (TGM2) and other genes involved in inflammatory response and autophagy in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. HIV+ subjects (n = 57) under antiretroviral therapy (ART) and healthy controls (n = 40) were enrolled. mRNA levels of 1-alpha-hydroxylase (CYP27B1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), TGM2, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 homolog (ATG5), and Beclin 1 (BECN1) were quantified by real-time PCR. In HIV+ subjects, 25(OH)D3 plasma levels were negatively correlated with time since HIV diagnosis. In PBMC from HIV+ subjects, increases in gene expression of TNF-α and IFN-γ in comparison to controls were observed. The highest increase in TNF-α transcripts was observed in HIV+ subjects with deficient 25(OH)D3 levels. Autophagy-related genes LC3, ATG5, and BECN1 were down-regulated in HIV+ subjects. Moreover, TGM2 transcripts were up-regulated in PBMC from HIV+ subjects with 25(OH)D3 deficiency. Changes observed in PBMC from HIV+ subjects appeared to be dependent on vitamin D status. The present results suggest that vitamin D deficiency is associated with changes in the expression of markers of inflammation and autophagy, resulting in immune cell dysfunction.

Highlights

Numerous clinical observations show that vitamin D deficiency may be associated with HIV infection [1,2,3]
In peripheral blood mononuclear cells (PBMC) from HIV+ subjects, we observed a significant increase in gene expression of both tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) when compared with PBMC from control subjects
A decrease in vitamin D levels is frequently reported during HIV infection, and vitamin D supplementation is frequently used in the clinical treatment of HIV+ subjects

Summary

Introduction

Numerous clinical observations show that vitamin D deficiency may be associated with HIV infection [1,2,3]. Vitamin D status may be related to side effects of antiretroviral therapy (ART) or other conditions associated with HIV infection [4,5,6,7,8,9]. The vitamin D active form, namely, 1,25(OH)2D3 is produced in the kidney and in extrarenal sites, including immune cells, thanks to the presence of enzyme 1-alpha-hydroxylase (CYP27B1) [13,14]. The presence of receptors for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been recognized in many cell types, including peripheral blood mononuclear cells (PBMC), with a relevant role in inflammatory response. The growing importance of the role of 1,25(OH)2D3 in both innate and adaptive immune responses has been highlighted [15]

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