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

• Published in: Mycopathologia (1975) Vol. 183; no. 5; pp. 739 - 749
• Main Authors: Jannuzzi, Grasielle Pereira, de Almeida, José Roberto Fogaça, dos Santos, Suelen Silvana, de Almeida, Sandro Rogério, Ferreira, Karen Spadari
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-10-2018; Springer; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Bone marrow; CCR7 protein; CD40 antigen; CD80 antigen; CD86 antigen; Cell activation; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - physiology; Eukaryotic Microbiology; Female; Interleukin 6; Kinases; Life Sciences; Lungs; Lymphocytes; Lymphocytes T; Mediation; Medical Microbiology; Membrane Proteins - metabolism; Mice, Inbred BALB C; Microbial Ecology; Microbiology; Mycoses; Mycosis; Notch protein; Original Article; Paracoccidioides - growth & development; Paracoccidioidomycosis - physiopathology; Pathogenesis; Plant Sciences; Receptors, Notch - metabolism; Secretase; Signal Transduction; South American blastomycosis; T cell receptors; T cells; T-Lymphocytes - immunology; Tumor necrosis factor-α; Yeasts; Paracoccidioidomycosis; Dendritic cells; Maturation; Notch; Paracoccidioides brasiliensis
• ISSN: 0301-486X; 1573-0832
• DOI: 10.1007/s11046-018-0276-3

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.