PMID: 

Infect Immun. 2013 Jan ;81(1):2-10. Epub 2012 Oct 15. PMID: 23071135

Abstract Title: 

Vitamin D rescues impaired Mycobacterium tuberculosis-mediated tumor necrosis factor release in macrophages of HIV-seropositive individuals through an enhanced Toll-like receptor signaling pathway in vitro.

Abstract: 

Mycobacterium tuberculosis disease represents an enormous global health problem, with exceptionally high morbidity and mortality in HIV-seropositive (HIV(+)) persons. Alveolar macrophages from HIV(+) persons demonstrate specific and targeted impairment of critical host cell responses, including impaired M. tuberculosis-mediated tumor necrosis factor (TNF) release and macrophage apoptosis. Vitamin D may promote anti-M. tuberculosis responses through upregulation of macrophage NO, NADPH oxidase, cathelicidin, and autophagy mechanisms, but whether vitamin D promotes anti-M. tuberculosis mechanisms in HIV(+) macrophages is not known. In the current study, human macrophages exposed to M. tuberculosis demonstrated robust release of TNF, IκB degradation, and NF-κB nuclear translocation, and these responses were independent of vitamin D pretreatment. In marked contrast, HIV(+) U1 human macrophages exposed to M. tuberculosis demonstrated very low TNF release and no significant IκB degradation or NF-κB nuclear translocation, whereasvitamin D pretreatment restored these critical responses. The vitamin D-mediated restored responses were dependent in part on macrophage CD14 expression. Importantly, similar response patterns were observed with clinically relevant human alveolar macrophages from healthy individuals and asymptomatic HIV(+) persons at high clinical risk of M. tuberculosis infection. Taken together with the observation that local bronchoalveolar lavage fluid (BALF) levels of vitamin D are severely deficient in HIV(+) persons, the data from this study demonstrate that exogenous vitamin D can selectively rescue impaired critical innate immune responses in vitro in alveolar macrophages from HIV(+) persons at risk for M. tuberculosis disease, supporting a potential role for exogenous vitamin D as a therapeutic adjuvant in M. tuberculosis infection in HIV(+) persons.

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PMID: 

Nutr Hosp. 2019 Oct 17 ;36(5):1205-1212. PMID: 31526009

Abstract Title: 

Effect of vitamin D3 supplementation on HIV-infected adults: a systematic reviewVitamin Dӡ Supplementation on HIV-Infected Adults: A Systematic Review.

Abstract: 

Introduction: much evidence confirms that vitamin D may be associated with an improvement in CD4 cell counts in HIV-infected individuals, where antiretroviral therapy (ART) is used and associated with decreased 25(OH)D levels. Objective: to carry out a systematic review on the effect of vitamin D supplementation on HIV-infected adult patients. Methods: the research was conducted in the databases Science Direct, PubMed, BVS, Scielo Cochrane and Periods, from February to April 2018, with publication limit from 2000 to 2018, without restriction of gender, ethnicity and involving individuals with age older than 18 years. To evaluate the quality of the studies, we used the protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Jadad scale. Results: the search initially resulted in 198 articles. After the selection process 5 articles were identified as eligible, where they highlight that vitamin D supplementation may be an associated and effective intervention to reduce hypovitaminosis. ART reduces vitamin D3 levels and changes its metabolism, being associated with the risk of mortality. However, adequate levels of 25(OH)D are positively associated with the number of CD4 + cells and the reduction of infection levels. Conclusion: vitamin D supplementation promotes immune recovery. However, the cases analysed were few, insufficient to fully confirm the benefits and recommend supplementation. Therefore, intervention studies are needed to elucidate the role of vitamin D in human protection against HIV infections.

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PMID: 

Int J Tuberc Lung Dis. 2019 08 1 ;23(8):919-923. PMID: 31533882

Abstract Title: 

Vitamin D deficiency is associated with tuberculosis infection among household contacts in Ulaanbaatar, Mongolia.

Abstract: 

Vitamin D deficiency (VDD) is a known risk factor for tuberculous infection. We investigated if VDD is a risk factor for tuberculous infection among the household contacts (HHCs) of patients with tuberculosis (TB) in Mongolia.All HHCs of TB patients diagnosed in Khan-Uul District, Mongolia, were enrolled. The serum level of 25-hydroxyvitamin D [25(OH)D] was detected and TB infection determined using QuantiFERON-TB Gold Plus (QFT-Plus). A tuberculin skin test (TST) reading>10 mm was considered to be positive. Epidemiological and bacteriological data were collected from routine surveillance of the National Tuberculosis Programme.Among study participants, 48.2% (135/285) were QFT-Plus-positive. Of QFT-positive HHCs, 77.0% (104/135) were TST-positive and the overall concordance of tests was low (κ 0.374,

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PMID: 

Int J Tuberc Lung Dis. 2020 Mar 1 ;24(3):278-286. PMID: 32228757

Abstract Title: 

Vitamin D status and latent tuberculosis infection: conversion in nursing homes, Spain.

Abstract: 

To examine the potential association between vitamin D (VitD) deficiency and latent tuberculosis infection (LTBI) and its effect on TB infection conversion (TBIC) incidence.We carried out a cross-sectional and prospective cohort study of nine pulmonary TB cases that occurred in 2015-2016 in five nursing homes and one mental disability institution in Castellon, Spain. QuantiFERON-TB Gold and the tuberculin skin test were used to detect LTBI and TBIC, respectively. Serum 25-hydroxyvitamin D was measured using chemiluminescence immunoassay. Poisson regression and inverse probability weighting were used for statistical analyses.The study included 448 residents, 341 staff members with 48 relatives of TB cases (participation rate 82%): of these, respectively 122 (27.2%), 37 (10.9%) and 7 (14.6%) were LTBI-positive; and respectively 22 (7.7%), 10 (3.8%) and 1 (3.7%) were TBIC-positive. LTBI was not associated with VitD status. Severe VitD deficiency (SVDD; defined as VitD level

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PMID: 

AIMS Microbiol. 2020 ;6(1):65-74. Epub 2020 Mar 13. PMID: 32226915

Abstract Title: 

Vitamin D level and it is association with the severity of pulmonary tuberculosis in patients attended to Kosti Teaching Hospital, Sudan.

Abstract: 

Globally, tuberculosis is one of the major causes of morbidity and mortality in many countries. Previous studies suggest that the incidence and severity of tuberculosis are associated with low levels of vitamin D (Vit D). Therefore, this study aimed to determine the occurrence and associated factors of vitamin D3 deficiency in pulmonary tuberculosis patients at White Nile State, Sudan. 101 individuals of diagnosed pulmonary tuberculosis patients (71 males and 30 females) and 100 non-TB controls (58 males and 42 females) were included in this study. Sputum samples were obtained from TB patients and subjected to examination for acid-fast bacilli (AFB) using Ziehl-Neelsen (ZN) stain and Gene Xpert analysis. Blood samples were collected from both groups and Serum 25(OH)-vitamin D3 was determined by an Enzyme-Linked Immunosorbent Assay. HIV infection in Tuberculosis (TB) group was also investigated using the immunochromatographic test. In our study, the majority of TB patients were suffered from TB relapse (36.6%); non-HIV infected individuals (99.1%) or showed a positive result for AFB (61.4%) in Gene Xpert analysis. Moreover, there is a significant difference in microscopy findings and bacillary levels of AFB, and Rifampicin (RIF) susceptibility pattern ofstrain among sputum samples of TB patients, P-values less 0.0001. Furthermore, we found that TB patients were suffered from vitamin D deficiency. In particular, the mean of vitamin D level was significantly much lower in TB patients (26.7± 1.6) compared to non-TB controls (117.3 ± 3.2), P-value equal 0.0001. Likewise, it's much lower in females, individuals of 21-40 years old, and patients with high bacillary levels or those infected by Rifampicin resistance strain. Accordingly, our study was highlighted the TB and Vit D deficiency relationship and showed the need for further studies to a better understanding of the impact of TB on Vit D level and investigate whether vitamin D supplementation can have a role in the prevention and treatment of tuberculosis.

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PMID: 

PLoS One. 2019 ;14(9):e0222878. Epub 2019 Sep 24. PMID: 31550271

Abstract Title: 

Vitamin D treatment of peripheral blood mononuclear cells modulated immune activation and reduced susceptibility to HIV-1 infection of CD4+ T lymphocytes.

Abstract: 

INTRODUCTION: Mucosal immune activation, in the context of sexual transmission of HIV-1 infection, is crucial, as the increased presence of activated T cells enhance susceptibility to infection. In this regard, it has been proposed that immunomodulatory compounds capable of modulating immune activation, such as Vitamin D (VitD) may reduce HIV-1 transmission and might be used as a safe and cost-effective strategy for prevention. Considering this, we examined the in vitro effect of the treatment of peripheral blood mononuclear cells (PBMCs) with the active form of VitD, calcitriol, on cellular activation, function and susceptibility of CD4+ T cells to HIV-1 infection.METHODS: We treated PBMCs from healthy HIV unexposed individuals (Co-HC) and frequently exposed, HIV-1 seronegative individuals (HESNs) from Colombia and from healthy non-exposed individuals from Canada (Ca-HC) with calcitriol and performed in vitro HIV-1 infection assays using X4- and R5-tropic HIV-1 strains respectively. In addition, we evaluated the activation and function of T cells and the expression of viral co-receptors, and select antiviral genes following calcitriol treatment.RESULTS: Calcitriol reduced the frequency of infected CD4+ T cells and the number of viral particles per cell, for both, X4- and R5-tropic viruses tested in the Co-HC and the Ca-HC, respectively, but not in HESNs. Furthermore, in the Co-HC, calcitriol reduced the frequency of polyclonally activated T cells expressing the activation markers HLA-DR and CD38, and those HLA-DR+CD38-, whereas increased the subpopulation HLA-DR-CD38+. Calcitriol treatment also decreased production of granzyme, IL-2 and MIP-1β by T cells and increased the transcriptional expression of the inhibitor of NF-kB and the antiviral genes cathelicidin (CAMP) and APOBEC3G in PBMCs from Co-HC.CONCLUSION: Our in vitro findings suggest that VitD treatment could reduce HIV-1 transmission through a specific modulation of the activation levels and function of T cells, and the production of antiviral factors. In conclusion, VitD remains as an interesting potential strategy to prevent HIV-1 transmission that should be further explored.

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PMID: 

Neurol Neuroimmunol Neuroinflamm. 2019 Nov ;6(6):e622. Epub 2019 Oct 3. PMID: 31582399

Abstract Title: 

Vitamin D enhances responses to interferon-β in MS.

Abstract: 

OBJECTIVE: To determine the effect of vitamin D3 on interferon-β (IFN-β) response and immune regulation in MS mononuclear cells (MNCs).METHODS: MNCs from 126 subjects, including therapy-naive patients with different forms of MS, plus patients with MS receiving IFN-β or glatiramer treatment, plus healthy controls were incubated in vitro with IFN-β-1b ± vitamin D3 (calcitriol). Activation of the IFN-β-induced transcription factor, p-Y-STAT1, and antiviral myxovirus A (MxA) protein was measured with flow cytometry and Western blots; serum proteins were measured with a customized 31-protein multiplex assay.RESULTS: Vitamin D enhanced in vitro IFN responses, as measured by induction of p-Y-STAT1 and MxA in MNCs, T cells, and monocytes. Vitamin D augmentation of IFN responses was seen in untreated and in IFN-β-1b-treated MS. The combination of vitamin D plus IFN-β reduced Th1 and Th17 cytokines, and increased Th2 responses, reversing the effect of IFN-β alone. Exacerbations and progression in untreated patients reduced the vitamin D enhancement of IFN responses. Vitamin D had less effect on IFN response in clinically stable glatiramer-treated than in IFN-β-treated patients.CONCLUSION: Vitamin D enhances IFN-β induction of multiple proteins and also reverses the Th1/Th2 bias in MS seen with IFN-β alone. The combination of vitamin D and IFN-β has potential benefit in ameliorating MS.

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PMID: 

J Cell Mol Med. 2020 Apr 13. Epub 2020 Apr 13. PMID: 32285621

Abstract Title: 

Calcitriol enhances Doxorubicin-induced apoptosis in papillary thyroid carcinoma cells via regulating VDR/PTPN2/p-STAT3 pathway.

Abstract: 

There is increasing evidence that vitamin D deficiency is the risk factor for multiple diseases, such as immune disorder, cardiovascular disease and cancer. Calcitriol is the active form of vitamin D with beneficial effects on anti-cancer by binding vitamin D receptor (VDR). The primary aim of this study was to investigate the role of Calcitriol on papillary thyroid carcinoma (PTC) and explore the possible mechanism. We found nuclear VDR expression in PTC samples was negatively correlated with STAT3 hyperphosphorylation that indicated worse PTC clinicopathologic characteristics. Calcitriol treatment up-regulated VDR and protein tyrosine phosphatase N 2 (PTPN2) expression, down-regulated signal transducers and activators of transcription (STAT3) phosphorylation and thereby facilitating chemotherapy drug Doxorubicin-induced apoptosis in PTC cell lines. However, the apoptosis-promoting effect of Calcitriol and Doxorubicin co-treatment was abrogated by STAT3 hyperphosphorylation, indicating suppression of STAT3 phosphorylation was essential for combined treatment of Calcitriol and Doxorubicin in PTC. Together, these results suggested that Calcitriol reinforced the sensitivity of PTC cells to Doxorubicin by regulating VDR/PTPN2/p-STAT3 signalling pathway.

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PMID: 

Front Immunol. 2019 ;10:2739. Epub 2019 Nov 22. PMID: 31824513

Abstract Title: 

Immunomodulatory Effects of Vitamin D in Pregnancy and Beyond.

Abstract: 

In addition to its role in calcium homeostasis and bone formation, a modulatory role of the active form of vitamin D on cells of the immune system, particularly T lymphocytes, has been described. The effects of vitamin D on the production and action of several cytokines has been intensively investigated in recent years. In this connection, deficiency of vitamin D has been associated with several autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), Hashimoto Thyroiditis (HT), and multiple sclerosis (MS). In a successful pregnancy, the maternal immune response needs to adapt to accommodate the semiallogeneic fetus. Disturbances in maternal tolerance are implicated in infertility and pregnancy complications such as miscarriages (RM) and preeclampsia (PE). It is well-known that a subset of T lymphocytes, regulatory T cells (Tregs) exhibit potent suppressive activity, and have a crucial role in curtailing the destructive response of the immune system during pregnancy, and preventing autoimmune diseases. Interestingly, vitamin D deficiency is common in pregnant women, despite the widespread use of prenatal vitamins, and adverse pregnancy outcomes such as RM, PE, intrauterine growth restriction have been linked to hypovitaminosis D during pregnancy. Research has shown that autoimmune diseases have a significant prevalence within the female population, and women with autoimmune disorders are at higher risk for adverse pregnancy outcomes. Provocatively, dysregulation of T cells plays a crucial role in the pathogenesis of autoimmunity, and adverse pregnancy outcomes where these pathologies are also associated with vitamin D deficiency. This article reviews the immunomodulatory role of vitamin D in autoimmune diseases and pregnancy. In particular, we will describe the role of vitamin D from conception until delivery, including the health of the offspring. This review highlights an observational study where hypovitaminosis D was correlated with decreased fertility, increased disease activity, placental insufficiency, and preeclampsia in women with APS.

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PMID: 

Photochem Photobiol Sci. 2017 Mar 16 ;16(3):381-398. PMID: 27922139

Abstract Title: 

Are low sun exposure and/or vitamin D risk factors for type 1 diabetes?

Abstract: 

The global variation in type 1 diabetes (T1D) incidence rates is one of the most significant observed for any non-communicable disease. Geographical patterns in incidence suggest that low sun exposure may contribute to the wide disparity, with incidence rates generally increasing with distance from the Equator. T1D development is associated with hyperactivity of the adaptive immune system leading to autoimmune destruction of insulin-secreting pancreaticβ cells. Both exposure to ultraviolet radiation (UVR) and vitamin D, with their known immunosuppressive effects, have the potential to delay or inhibit the disease. Efforts to confirm the role of UVR by vitamin D dependent and independent pathways in the pathogenesis of T1D have been challenged byinconsistent results among studies. Human observational studies and animal and in vitro experiments indicate that at least some of the benefits of sun exposure come from improved vitamin D status. There is no evidence of benefit for T1D risk of vitamin D supplementation during pregnancy at current recommended levels (400 IU per day); but some evidence supports that higher sun exposure and/or vitamin D sufficiency in pregnancy, or supplementation in early life, decreases T1D risk. Further research is required to confirm an association between UVR exposure and T1D and clarify the mechanisms involved.

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