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

饮食中缺乏维生素 D3 可增强小鼠对亚马逊利什曼原虫 (Leishmania) 感染的抵抗力

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作者:Izabella Pereira da Silva Bezerra, Gabriel Oliveira-Silva, Danielle Sophia Ferreira Santos Braga, Mirian França de Mello, Juliana Elena Silveira Pratti, Joyce Carvalho Pereira, Alessandra Marcia da Fonseca-Martins, Luan Firmino-Cruz, Diogo Maciel-Oliveira, Tadeu Diniz Ramos, André Macedo Vale, Danie

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.

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