| Autor: |
Gomes, Rodrigo Saar, Silva, Muriel Vilela Teodoro, dos Santos, Jéssica Cristina, van Linge, Christine, Reis, Juliana Machado, Teixeira, Mauro Martins, Pinto, Sebastião Alves, Dorta, Miriam Leandro, Bai, Xiyuan, Chan, Edward D., Dinarello, Charles A., Oliveira, Milton Adriano Pelli, Joosten, Leo A. B., Ribeiro-Dias, Fátima |
| Zdroj: |
Infection and Immunity; March 2018, Vol. 86 Issue: 5 |
| Abstrakt: |
ABSTRACTVisceral leishmaniasis (VL) is a chronic parasitic disease caused by Leishmania infantumin the Americas. During VL, several proinflammatory cytokines are produced in spleen, liver, and bone marrow. However, the role of interleukin-32 (IL-32) has not been explored in this disease. IL-32 can induce production of proinflammatory cytokines in innate immune cells and polarize the adaptive immune response. Herein, we discovered that L. infantumantigens induced expression of mRNA mainly for the IL-32γ isoform but also induced low levels of the IL-32β transcript in human peripheral blood mononuclear cells. Furthermore, infection of human IL-32γ transgenic mice (IL-32γTg mice) with L. infantumpromastigote forms increased IL-32γ expression in the spleen and liver. Interestingly, IL-32γTg mice harbored less parasitism in the spleen and liver than wild-type (WT) mice. In addition, IL-32γTg mice showed increased granuloma formation in the liver compared to WT mice. The protection against VL was associated with increased production of nitric oxide (NO), interferon gamma (IFN-γ), IL-17A, and tumor necrosis factor alpha by splenic cells restimulated ex vivowith L. infantumantigens. In parallel, there was an increase in the number of Th1 and Th17 T cells in the spleens of IL-32γTg mice infected with L. infantum. IL-32γ induction of IFN-γ and IL-17A expression was found to be essential for NO production by splenic cells of infected animals. These data indicate that IL-32γ potentiates the Th1/Th17 immune response during experimental VL, thus contributing to the control of L. infantuminfection. |
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