Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro

Autor(es)

da Silva, Thiago Aparecido ; Roque-Barreira, Maria Cristina ; Casadevall, Arturo ; Almeida, Fausto

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 6, OCT 24 2016.
• Citações Web of Science: 14

Resumo

Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated. Herein, we verified that EVs from P. brasiliensis induce the production of proinflammatory mediators by murine macrophages in a dose-dependent manner. Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. Our results suggest that EVs from P. brasiliensis can modulate the innate immune response and affect the relationship between P. brasiliensis and host immune cells. (AU)

• Processo FAPESP: 16/03322-7 - Papel de galectina-3 na infecção por Cryptococcus neoformans
• Beneficiário: Fausto Bruno dos Reis Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/10741-8 - Efeito da inibição de N-glicosilação sobre o perfil transcricional e proteômico de Paracoccidioides brasiliensis
• Beneficiário: Fausto Bruno dos Reis Almeida
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/04088-0 - Lectinas de patógenos
• Beneficiário: Maria Cristina Roque Antunes Barreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/04877-2 - Delineamento de novas estratégias terapêuticas, baseadas em reconhecimento de carboidratos, contra a criptococose
• Beneficiário: Thiago Aparecido da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado