MR1 blockade drives differential impact on integrative signatures based on circuits of circulating immune cells and soluble mediators in visceral leishmaniasis

MR1 阻断对内脏利什曼病中基于循环免疫细胞和可溶性介质回路的整合特征产生不同的影响

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作者:Luana Oliveira Borges-Fernandes #, Marcela de Lima Moreira #, Victória Hellena Silva Pereira, Marcelo Antônio Pascoal-Xavier, Ágata Lopes Ribeiro, Ismael Artur da Costa-Rocha, Ludmila Rosa Lopes, Guilherme Telles Cristo Moreira, Márcio Sobreira da Silva Araújo, Andréa Teixeira-Carvalho, Joaquim Pedr

Conclusion

These data corroborate the hypothesis that MR1-restricted responses are associated to a protective role during Leishmania infection.

Methods

Here, we describe the impact of the MR1-blockage on L. infantum internalization on the functional profile of circulating neutrophils and monocytes as well as the impact of the MR1-blockage on the soluble mediator signatures of in vitro whole blood cultures.

Results

Overall, our data showed that VL patients presents higher percentage of activated neutrophils than asymptomatic and non-infected controls. In addition, MR1 blockade led to lower TNF-α and TGF-β production by non-activated neutrophils from asymptomatic individuals. Moreover, TNF-α and IL-10 production by monocytes was higher in VL patients. In the analysis of soluble mediators produced in vitro, MR1-blockade induced a decrease of IFN-γ and an increase of IL-10, IL-27 and IL-33 in the cell cultures of AS group, a cytokine pattern associated with type 2 deleterious response.

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