Dietary Vitamin D3 Deficiency Increases Resistance to Leishmania (Leishmania) amazonensis Infection in Mice

Abstract

The leishmaniases are a group of diseases caused by Leishmania parasites, which have different clinical manifestations. Leishmania (Leishmania) amazonensis is endemic in South America and causes cutaneous leishmaniasis (CL), which can evolve into a diffuse form, characterized by an anergic immune response. Since the leishmaniases mainly affect poor populations, it is important to understand the involvement of immunonutrition, how the immune system is modulated by dietary nutrients and the effect this has on Leishmania infection. Vitamin D3 (VitD) is an immunonutrient obtained from diet or endogenously synthesized, which suppresses Th1 and Th17 responses by favoring T helper (Th) 2 and regulatory T cell (Treg) generation. Based on these findings, this study aims to evaluate dietary VitD influence on L. (L.) amazonensis experimental infection in C57BL/6 and BALB/c mice. Thus, C57BL/6 and BALB/c VitD deficient (VDD) mice were generated through dietary VitD restriction 45 days prior to infection. Both strains of VDD mice showed a more controlled lesion development compared to mice on a regular diet (Ctrl). There were no differences in serum levels of anti- Leishmania IgG1 and IgG2a, but there was a decrease in IgE levels in BALB/c VDD mice. Although CD4 + T cell number was not changed, the CD4 + IFN-y + T cell population was increased in both absolute number and percentage in C57BL/6 and BALB/c VDD mice compared to Ctrl mice. There was also no difference in IL-4 and IL-17 production, however, there was reduction of IL-10 production in VDD mice. Together, our data indicate that VitD contributes to murine cutaneous leishmaniasis susceptibility and that the Th1 cell population may be related to the resistance of VDD mice to L. (L.) amazonensis infection.

Inoculation of the Leishmania infantum HSP70-II Null Mutant Induces Long-Term Protection against L. amazonensis Infection in BALB/c Mice

“…This differential effect of the infectious dose on the evolution of the disease was not observed in other vaccine models such as C57BL/6 mice inoculated with a total protein-based vaccine LaAg [45]. On the other hand, the influence of the L. amazonensis inoculum size in the progression of the disease was previously reported for different murine models [6] and also influenced the studies regarding the effects of immunonutrition in the outcome of infection in BALB/c and C57BL/6 mice [46]. In the same direction, the protective effect of a vaccine based on the intranasal administration of extracellular serine proteases is inversely proportional to the infectivity of the inoculum [13].…”

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

“…In agreement with this study, L. mexicana -infected mice treated with vitamin D exhibit a reduction in lesion size (Ramos-Martínez et al ., 2013). In contrast, L. amazonensis- infected mice that received a vitamin D-deficient diet controlled the lesion development better than mice that received a regular diet (Bezerra et al ., 2019). In addition, C57BL/6 mice deficient for the VDR and infected with L. major developed significantly smaller lesions and had a reduced inflammatory process when compared to C57BL/6 WT mice (Whitcomb et al ., 2012).…”

“…All these effects promoted by vitamin D in the immune system are unfavourable to the development of an effective immune response against Leishmania spp., which thus favours the parasite growth and the consequent disease progression in the host. Our previous data have demonstrated that in the absence of vitamin D in the diet, there is a decrease in the lesion size of infected mice due to an increase of Th1 cells (Bezerra et al ., 2019). However, in this paper, we have investigated the vitamin D role at the host cell level, and we suggest that vitamin D (D 2 and D 3 ) can directly cause a slight increase in the control of the parasite load.…”

“…In accordance with this, Rodriguez-Cortes and colleagues have shown in a cohort study that dogs naturally infected with Leishmania and exhibiting symptoms of the disease presented lower vitamin D levels in the serum compared with asymptomatic or non-infected animals (Rodriguez-Cortes et al ., 2017). In contrast, Leishmania amazonensis -infected mice receiving a vitamin D-deficient diet control lesion development better than those receiving a regular diet, which was shown to be due to the involvement of Th1 cells in both C57BL/6 and BALB/c mice (Bezerra et al ., 2019). Furthermore, during L. major infection, C57BL/6 mice deficient for the vitamin D receptor (VDR knockout) developed significantly smaller lesions, with a reduced inflammatory response and healing time 3 weeks faster than wild-type (WT) C57BL/6 mice.…”

Vitamin d and leishmaniasis: Neither seasonal nor risk factor in canine host but potential adjuvant treatment through cbd103 expression

“…Some observational, preclinical, and clinical studies have shown that low levels of VitD increase the risk of developing multiple diseases in humans (cancer, diabetes, autoimmune diseases and infectious diseases such as toxoplasmosis, AIDS, influenza or malaria) [ 26 – 32 ]. However, few studies have investigated VitD and leishmaniasis, with contradictory results depending on the animal model and Leishmania species [ 33 – 36 ]. We previously showed, for the first time, that dogs with clinical leishmaniasis and also those with asymptomatic infection presented lower VitD serum concentration than non-infected dogs.…”