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Notch Signaling is Required for Dendritic Cell Maturation and T Cell Expansion in Paracoccidioidomycosis

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Abstract

The Notch signaling pathway participates in several cellular functional aspects. This signaling has an important role in targeting both DC maturation and DC-mediated T cell responses. Thus, it is essential to investigate the influence of this signaling pathway in the role played by DCs in the pathogenesis of experimental paracoccidioidomycosis. This disease is a granulomatous and systemic mycosis that mainly affects lung tissue and can spread to any other organ and system. In this study, we demonstrated that bone marrow-derived DCs infected with yeasts from Paracoccidioides brasiliensis strain 18 performed efficiently their maturation after the activation of Notch signaling, with an increase in CD80, CD86, CCR7, and CD40 expression and the release of cytokines such as IL-6 and TNF-α. We observed that the inhibition of the γ-secretase DAPT impaired the proliferation of T cells induced by DC stimulation. In conclusion, our data suggest that Notch signaling contributes effectively to the maturation of DCs and the DC-mediated activation of the T cell response in P. brasiliensis infections.

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Acknowledgements

This work was supported by grants from FAPESP (Process 2015/17338-0) and CNPq.

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Funding

This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP, and from Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq.

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  1. Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas da, Universidade de São Paulo, Avenida Professor Lineu Prestes, 580, Bloco 17, Butantã, São Paulo, SP, Brazil

    Grasielle Pereira Jannuzzi, José Roberto Fogaça de Almeida, Suelen Silvana dos Santos & Sandro Rogério de Almeida

  2. Instituto de Ciências Ambientais, Químicas e Farmacêuticas da, Universidade Federal de São Paulo, Diadema, Brazil

    Karen Spadari Ferreira

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  1. Grasielle Pereira Jannuzzi
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  2. José Roberto Fogaça de Almeida
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Jannuzzi, G.P., de Almeida, J.R.F., dos Santos, S.S. et al. Notch Signaling is Required for Dendritic Cell Maturation and T Cell Expansion in Paracoccidioidomycosis. Mycopathologia 183, 739–749 (2018). https://doi.org/10.1007/s11046-018-0276-3

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