title: Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro.
abstract: 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.
authors: Ribeirao Preto Medical School, Department of Cellular and Molecular Biology, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors: Thiago Aparecido
authors: TA
authors: da Silva
authors: Ribeirao Preto Medical School, Department of Cellular and Molecular Biology, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors: Maria Cristina
authors: MC
authors: Roque-Barreira
authors: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health Baltimore, MD, USA.
authors: Arturo
authors: A
authors: Casadevall
authors: Ribeirao Preto Medical School, Department of Cellular and Molecular Biology, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors: Fausto
authors: F
authors: Almeida
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D010228:Paracoccidioides / Q000276:immunology*
chemical_list: D000946:Antigens, Fungal; D016207:Cytokines