Vitamin D increases killing of intracellularLeishmania amazonensis in vitroindependently of macrophage oxidative mechanisms

Abstract

Vitamin D has been reported to activate macrophage microbicidal mechanisms by inducing the production of antimicrobial peptides and nitric oxide (NO), but conversely has been shown to contribute to a greater susceptibility to Leishmania amazonensis infection in mice. Thus, this study aimed to evaluate the role of vitamin D during intracellular infection with L. amazonensis by examining its effect on macrophage oxidative mechanisms and parasite survival in vitro. Vitamins D2 and D3 significantly inhibited promastigote and amastigote growth in vitro. Vitamin D3 was not able to induce NO and reactive oxygen species (ROS) production in uninfected macrophages or macrophages infected with L. amazonensis. In addition, vitamin D3 in combination with interferon (IFN)-γ did not enhance amastigote killing and in fact, significantly reduced NO and ROS production when compared with the effect of IFN-γ alone. In this study, we demonstrated that vitamin D directly reduces parasite growth in infected macrophages (approximately 50–60% at 50 μm) but this effect is independent of the activation of macrophage oxidative mechanisms. These findings will contribute to a better understanding of the role of vitamin D in cutaneous leishmaniasis.

Utility of vitamin D serum evaluation and supplementation in dogs and cats’ medical routine: a review

“…On the other hand, VDR expression was associated with inhibition of the leishmanicidal activity of macrophages, as VDR-knockout mice showed greater resistance to infection by Leishmania major (Ehrchen et al, 2007). The incubation of macrophages with vitamin D reduced parasitic growth in the cells contaminated by Leishmania amazonenses (Machado et al, 2020), whereas mice treated every 48h for 12 weeks with calcitriol showed a drastic reduction in skin lesions caused by infection with Leishmania sp. (Ramos-Martínez et al, 2013).…”

The Possible Role of Selected Vitamins and Minerals in the Therapeutic Outcomes of Leishmaniasis

“…Moreover, there has been no link among the status of vitamin D and the cell immune response to Leishmania. [84] Despite the major role of vitamin D in tissue healing, however, it had no discernible effect on the parasite's viability in individuals with active leishmaniasis [85]. Nitrous oxide (NO) is widely considered as the primary antimicrobial compound used to inhibit Leishmania major through Interferon-γ activated macrophages in the animal model.…”

Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

“…Endogenous calcitriol was also found to decrease the humoral IgE and IgG1 response to parasite infection [ 140 ]. Similarly, in the case of Leishmania amazonensis, vitamin D was shown to increase susceptibility to parasite infection in mice, but in an in vitro study, the reduction of parasite growth in infected macrophages in a process independent of macrophage oxidative mechanisms was demonstrated [ 141 ]. In the case of Plasmodium spp., vitamin D was found to inhibit parasite growth extensively during the acute phase and subsequent parasite growth, forming a mildly delayed peak [ 142 , 143 ].…”

“…It should be emphasized that high doses required to obtain positive immune effects in the host organism can result in severe side effects, including hypercalcemia [ 144 ]. Vitamin D deficiency was correlated with higher Toxoplasma infection prevalence, but the effects promoted by vitamin D in the immune system, including decreasing production of interleukin 12 (IL-12) and tumor necrosis factor-alpha (TNF-α) by monocytes and macrophages, and IFN-γ by CD4+ T cells, decreasing the differentiation of Th1 cells and increasing the differentiation of regulatory T cells, are unfavorable to the development of an effective immune response against the protozoan parasites [ 141 ]. Nevertheless, the in vitro studies revealed the potential of vitamin D in toxoplasmosis treatment.…”