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.

Highlights

  • The leishmaniases are a group of diseases caused by protozoans of the Leishmania genus, which are transmitted to mammalian hosts by female sandflies of the Phlebotominae family

  • The development of L. (L.) amazonensis infection was evaluated in partially susceptible C57BL/6 and susceptible BALB/c mice submitted to dietary Vitamin D3 (VitD) restriction (VDD) or fed a regular diet (Ctrl)

  • In C57BL/6 VitD deficient (VDD) the lesions began to resolve by day 60, whereas in the compared to mice on a regular diet (Ctrl) mice this did not occur until day 75

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Summary

Introduction

The leishmaniases are a group of diseases caused by protozoans of the Leishmania genus, which are transmitted to mammalian hosts by female sandflies of the Phlebotominae family. 0.7 to 1 million new cases occur worldwide and clinical manifestations are divided into cutaneous and the lethal visceral leishmaniasis (VL) (Burza et al, 2018). Cutaneous leishmaniasis (CL) is generally characterized by a single self-healing ulcer. Depending on the parasite species involved in infection and on the host immune status, it can evolve into a more severe manifestation (Scott and Novais, 2016). Leishmania (Leishmania) amazonensis, a species of the L. (L.) mexicana complex, is endemic in many South American countries and can cause diffuse CL, characterized by an anergic immune response and excess of parasites in multiple lesions. (L.) amazonensis have been reported previously (Silveira et al, 2004) Cases of VL caused by L. (L.) amazonensis have been reported previously (Silveira et al, 2004)

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