The Critical Role of Notch1-TLR 4 Signaling in the Inflammatory and Fungicidal Activity of Macrophages Against Paracoccidioides brasiliensis Strain Pb18

Autor(es)

Dal'Mas Romera, Lavinia Maria ; Kaihami, Gilberto Hideo ; Jannuzzi, Grasielle Pereira ; Fogaca de Almeida, Jose Roberto ; de Almeida, Sandro Rogerio

• Tipo de documento: Artigo Científico
• Fonte: Mycopathologia; v. 182, n. 9-10, p. 797-807, OCT 2017.
• Citações Web of Science: 2

Resumo

Paracoccidioidomycosis is a systemic mycosis of deep nature that primarily affects the lung and can spread via lymphatic and hematogenous to other organs and tissues. It is mainly caused by Paracoccidioides brasiliensis fungus which exhibits thermal dimorphism. The innate immune system mediated by macrophages is extremely important for the control of infection and is involved in the induction and regulation of immune/inflammatory response. These cells are able to recognize pathogens through pattern recognition receptors (PRRs) such as Toll-like receptors (TLR). Beyond these PRRs, the importance of Notch signaling has recently been demonstrated in the innate immune system and the regulation of macrophage activity. Our data demonstrate that the Pb18 strain of P. brasiliensis is able to activate the transcription of Notch1 receptor in J774 macrophages. Activation of this receptor with also activation of TLR 4 (via LPS) induces IL-6 production, which favors the pathogenesis. By using a gamma-secretase pharmacological inhibitor (DAPT) for inhibiting the activation of Notch1 receptor on macrophages, it is possible to observe the decreased fungal burden, less production of IL-6, and increased TNF-alpha and phagocytosis. Taken together, these results showed that Pb18 is able to induce the transcription of Notch1 receptor on macrophages and may provide a new immunity study approach in experimental paracoccidioidomycosis. (AU)

• Processo FAPESP: 12/14955-0 - Caracterização da inter-relação entre as vias de sinalização Notch e TLR na paracoccidioidomicose experimental
• Beneficiário: Lavínia Maria Dalmas Romera
• Modalidade de apoio: Bolsas no Brasil - Doutorado