Vitamin D3 compounds regulate human immunodeficiency virus type 1 replication in U937 monoblastoid cells and in monocyte-derived macrophages

Pauza, C. David; Kornbluth, Richard S.; Emau, Peter; Richman, Douglas D.; Deftos, Leonard J.

doi:10.1002/jlb.53.2.157

Cited by 25 publications

(14 citation statements)

References 23 publications

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“…Vitamin D deficiency is associated with susceptibility to active TB in both the absence and the presence of HIV infection, but the association is stronger (24), suggesting a potential direct causal relationship between vitamin D deficiency and susceptibility to active TB. In HIV-infected people, vitamin D might also indirectly enhance antimycobacterial immunity by slowing progression of HIV disease (25,26), although studies investigating the effect of vitamin D metabolites on HIV replication in vitro report conflicting results (27)(28)(29)(30)(31). It is biologically plausible, therefore, that vitamin D deficiency impairs antimycobacterial responses in HIV-infected adults and that this phenomenon explains the association between vitamin D deficiency and susceptibility to active TB that we report here.…”

Section: Discussionmentioning

confidence: 70%

Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa

Martineau

Nhamoyebonde

Oni

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

183

181

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Vitamin D deficiency is associated with susceptibility to tuberculosis (TB) in HIV-uninfected people in Europe, but it is not known whether such an association exists among HIV-infected people in subtropical Africa. We conducted a cross-sectional study to determine whether vitamin D deficiency was associated with susceptibility to active TB in and HIV-infected (n = 174) black Africans in Cape Town, South Africa. We also investigated whether there was evidence of seasonal variation in vitamin D status and TB notifications in this setting over an 8-y period.nmol/L) was present in 232 (62.7%) of 370 participants and was associated with active TB in both HIV-uninfected (odds ratio = 5.2, 95% confidence interval: 2.8-9.7; P < 0.001) and HIV-infected (odds ratio = 5.6, 95% confidence interval: 2.7-11.6; P < 0.001) people. We have previously reported that vitamin D deficiency is associated with susceptibility to TB in London and that this association is modified by polymorphisms in the vitamin D receptor and vitamin D binding protein (8,9). We have also shown that in vivo vitamin D supplementation enhances immunity to mycobacteria both in healthy people (10) and in a genetically defined subgroup of patients with active TB (11). Reports of seasonal variation in the prevalence of vitamin D deficiency (12) and TB incidence (13) in the United Kingdom provide further evidence that low vitamin D status may compromise antimycobacterial immunity in this setting.The prevalence of profound vitamin D deficiency among TB patients in tropical Africa is much lower than in Europe [reported in 0.3-11.2% of patients with TB in tropical Africa (14-17) vs. 64-84% of patients with TB in ]. The prevalence of vitamin D deficiency in TB patients with and without HIV infection in subtropical Africa has not previously been reported. There is particularly good reason to investigate this question in Cape Town, South Africa, because TB incidence in Cape Town is higher than elsewhere in South Africa (21) and the ability of sunlight to synthesize vitamin D is compromised during the winter in Cape Town (latitude 33°south) but not in Johannesburg (latitude 26°south) (22). We therefore conducted an observational study to determine whether vitamin D deficiency is associated with susceptibility to active TB in HIVinfected and HIV-uninfected adults in Cape Town and to investigate whether there is evidence of seasonal variation in vitamin D status and TB notifications in this setting.

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Section: Discussionmentioning

confidence: 70%

Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa

Martineau

Nhamoyebonde

Oni

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

183

181

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“…However, VD3 has also been shown to control the proliferation of microorganisms [15][16][17][18][19][20], being contrary of immunosuppression. Previous studies reported that VD inhibits the growth of Pf in vitro [25] and experimental cerebral malaria induced by P. berghei ANKA infection in mice [26].…”

Section: Accepted Manuscriptmentioning

confidence: 97%

“…Instead, there are numerous reports showing the potential of VD to inhibit microorganism proliferation [15][16][17][18][19][20], particularly in the case of tuberculosis and other mycobacterial infections [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Dual antiplasmodial activity of vitamin D3 and its analog, 22-oxacalcitriol, by direct and indirect mechanisms

Yamamoto

Iwagami

Seki

et al. 2017

Parasitology International

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Recent evidence suggests that 1α,25-dihydroxyvitamin D3 (calcitriol, VD3), the active form of vitamin D (VD), can inhibit the proliferation of microorganisms. In the present study, we conducted in vitro experiments and utilized in vivo murine models to investigate the antimalarial activity of VD3 and its analog, 22-oxacalcitriol (22-OCT), which was designed to cause less hypercalcemia than VD3. VD3 and 22-OCT treatments effectively resolved a Plasmodium chabaudi (Pc) infection in wild-type mice. Reduced parasitemia was observed during the acute phase of infection in the presence of VD3 and 22-OCT, followed by a delayed peak during the chronic stage of infection. Some anti-Pc activity was observed in VD receptor knockout (KO) mice. VD3 and 22-OCT also completely inhibited the proliferation of P. falciparum (Pf) in human red blood cells in vitro. Plasma levels of interferon (IFN)-γ in VD3-treated B10 and B6 mice were lower than those in vehicle-treated animals, and VD3 resolved a Pc infection in IFN-γ-KO mice, which greatly improved survival. These data suggest that the protective effects of VD3 are elicited through an IFN-γ-independent mechanism. Effective antiplasmodial doses of VD3 and 22-OCT resulted in a loss of body weight in mice. This loss in body weight occurred concomitantly with the development of hypercalcemia. Zoledronic acid partially attenuated VD3-induced hypercalcemia and abrogated the antiparasitic effects of VD3. This study highlights a potential therapeutic role for VD3 in the treatment of malarial infections and shows that hypercalcemia is excellent indicator of the antiplasmodial activity of VD3.

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“…Additionally, women with low levels of 25D3 have an increased risk of HIV disease progression [22] and infants born to HIV-infected mothers with low 25D3 levels have an increased risk of HIV infection and increased mortality [23]. Although 25D3 has no direct anti-mycobacterial or antiretroviral effect, its hormonally active form, 1,25D3, modulates the immune response and has been shown to exert both anti-mycobacterial [24]–[27] and anti-HIV effects [27], [28] in vitro .…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Inhibits Human Immunodeficiency Virus Type 1 and Mycobacterium tuberculosis Infection in Macrophages through the Induction of Autophagy

2012

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Low vitamin D levels in human immunodeficiency virus type-1 (HIV) infected persons are associated with more rapid disease progression and increased risk for Mycobacterium tuberculosis infection. We have previously shown that 1α,25-dihydroxycholecalciferol (1,25D3), the active form of vitamin D, inhibits HIV replication in human macrophages through the induction of autophagy. In this study, we report that physiological concentrations of 1,25D3 induce the production of the human cathelicidin microbial peptide (CAMP) and autophagic flux in HIV and M. tuberculosis co-infected human macrophages which inhibits mycobacterial growth and the replication of HIV. Using RNA interference for Beclin-1 and the autophagy-related 5 homologue, combined with the chemical inhibitors of autophagic flux, bafilomycin A1, an inhibitor of autophagosome-lysosome fusion and subsequent acidification, and SID 26681509 an inhibitor of the lysosome hydrolase cathepsin L, we show that the 1,25D3-mediated inhibition of HIV replication and mycobacterial growth during single infection or dual infection is dependent not only upon the induction of autophagy, but also through phagosomal maturation. Moreover, through the use of RNA interference for CAMP, we demonstrate that cathelicidin is essential for the 1,25D3 induced autophagic flux and inhibition of HIV replication and mycobacterial growth. The present findings provide a biological explanation for the benefits and importance of vitamin D sufficiency in HIV and M. tuberculosis-infected persons, and provide new insights into novel approaches to prevent and treat HIV infection and related opportunistic infections.

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Vitamin D3 compounds regulate human immunodeficiency virus type 1 replication in U937 monoblastoid cells and in monocyte-derived macrophages

Cited by 25 publications

References 23 publications

Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa

Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa

Dual antiplasmodial activity of vitamin D3 and its analog, 22-oxacalcitriol, by direct and indirect mechanisms

Vitamin D Inhibits Human Immunodeficiency Virus Type 1 and Mycobacterium tuberculosis Infection in Macrophages through the Induction of Autophagy

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