Protection against Paracoccidioides brasiliensis infection in mice treated with modulated dendritic cells relies on inhibition of interleukin-10 production by CD8+ T cells

用调节树突状细胞治疗的小鼠对巴西副球孢子菌感染的保护依赖于抑制 CD8+ T 细胞产生白细胞介素 10

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作者:Thiago Alves da Costa, Rosária Di Gangi, Paula Martins, Ana Leda Figueiredo Longhini, Fábio Zanucoli, Alexandre Leite Rodrigues de Oliveira, Dagmar Ruth Stach-Machado, Eva Burger, Liana Verinaud, Rodolfo Thomé

Abstract

Paracoccidioidomycosis is a systemic infection prevalent in Latin American countries. Disease develops after inhalation of Paracoccidioides brasiliensis conidia followed by an improper immune activation by the host leucocytes. Dendritic cells (DCs) are antigen-presenting cells with the unique ability to direct the adaptive immune response by the time of activation of naive T cells. This study was conducted to test whether extracts of P. brasiliensis would induce maturation of DCs. We found that DCs treated with extracts acquired an inflammatory phenotype and upon adoptive transfer conferred protection to infection. Interestingly, interleukin-10 production by CD8(+) T cells was ablated following DC transfer. Further analyses showed that lymphocytes from infected mice were high producers of interleukin-10, with CD8(+) T cells being the main source. Blockage of cross-presentation to CD8(+) T cells by modulated DCs abolished the protective effect of adoptive transfer. Collectively, our data show that adoptive transfer of P. brasiliensis-modulated DCs is an interesting approach for the control of infection in paracoccidioidomycosis.

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