NLRP3 inflammasome is involved in the recognition of Paracoccidioides brasiliensis by human dendritic cells and in the induction of Th17 cells

Autor(es)

de Castro, Livia Furquim ^[1] ; Alegrini Longhi, Larissa Nara ^[1] ; Paiao, Munir Regini ^[1] ; Justo-Junior, Amauri da Silva ^[1] ; de Jesus, Marcelo Bispo ^[2] ; de Souza Lima Blotta, Maria Heloisa ^[1] ; Mamoni, Ronei Luciano ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Fac Med Sci, Dept Clin Pathol, BR-13083970 Campinas, SP - Brazil

^[2] Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

^[3] FMJ, Dept Morphol & Basic Pathol, Jundiai, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Infection; v. 77, n. 2, p. 137-144, AUG 2018.
• Citações Web of Science: 2

Resumo

Objectives: To investigate the involvement of NLRP3 in the effector functions of human dendritic cells (DCs) in response to Paracoccidioides brasiliensis yeast cells (Pb) and to evaluate its role in the modulation of the adaptive immune response. Methods: DCs were differentiated from purified peripheral blood monocytes and analyzed in relation to the participation of TLR-2,dectin-1, and Syk in Pb recognition, as well as, the indirect mechanisms (Reactive Oxygen Species production, endosome acidification, or K+ efflux) involved in NLRP3 inflammasome activation after the stimulus with Pb. Additionally, we analyzed the role of NLRP3 in the activation of T cells. Results: Our results demonstrated that the NLRP3 inflammasome activation and cytokines production by DCs are dependent on ROS generation, endosome acidification, and K+ efflux and involve the Pb recognition by dectin-1 and Syk phosphorylation. Our data also demonstrate that the NLRP3 inflammasome is essential for the activation/expansion of Th1/Th17 cells and its inhibition leads to an increased frequency of Th2 and Treg cells. Conclusion: Altogether our data indicated that activation of NLRP3 presents an important role in both the induction of the initial inflammatory response and in the development of the acquired immune response associated with resistance to infection. (C) 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 08/57906-3 - Instituto Nacional de Fotônica Aplicada à Biologia Celular - INFABIC
• Beneficiário: Hernandes Faustino de Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/03673-6 - Estudo da participação do inflamassoma NLRP3 na resposta inflamatória induzida pelo fungo dimórfico Paracoccidioides brasiliensis
• Beneficiário: Lívia Furquim de Castro
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 13/24286-0 - Estudo da participação do inflamassoma NLRP3 e das citocinas da família da IL-1 na resposta inflamatória induzida pelos fungos patogênicos Paracoccidioides brasiliensis e Candida albicans
• Beneficiário: Ronei Luciano Mamoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular