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- W2743307237 abstract "Abstract Paracoccidioidomycosis (PCM) is a systemic mycosis of deep nature and granulomatosis that preferably affects the lung tissue and can disseminate to other organs and tissues, and is caused by Paracoccidioides brasiliensis, a thermal dimorphic fungus. Macrophages, cells that have an important role in regulation of immune response, recognize this fungus through pattern recognition receptors (PRR), such as Toll-like receptor (TLR). Recently it has been demonstrated the importance of Notch receptors in regulation the activity of macrophages in immune response, and also that TLR acts together with Notch receptor. Given that Notch and TLR signaling are involved in modulating macrophage function, we evaluated the ability of the fungus modulate the activation of these pathway. Our data demonstrated that activation of TLR4 in macrophages is dependent of Notch 1 receptor, and promotes an increase of IL-6, this cytokine is important to the establishment of PCM. We also observed that the increased level of IL-6 is associated with decrease of TNF-alfa, and phagocitosys. Moreover, when Notch receptor was inhibited, we observed a decreased activation of TLR4 and TLR2, decreased of IL-6 and fungal load, but an increase of TNF-alfa and phagocitosys. We also observed a decrease of fungal load in bone marrow macrophages from TLR4 knockout mice. Similar results are seen in vivo with Notch inhibition, with a decrease of fungal load. This results suggest that P. brasiliensis utilizes Notch-TLR signaling as an escape mechanism." @default.
- W2743307237 created "2017-08-17" @default.
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- W2743307237 date "2016-05-01" @default.
- W2743307237 modified "2023-09-27" @default.
- W2743307237 title "Characterization of notch and toll-like receptor interactions in macrophages against <i>Paracoccidioides brasiliensis</i>" @default.
- W2743307237 doi "https://doi.org/10.4049/jimmunol.196.supp.205.16" @default.
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