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Published on: September 18, 2020
Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro
Thiago Aparecido da Silva1, Maria Cristina Roque-Barreira1, Arturo Casadevall2
1Ribeirao Preto Medical School, Department of Cellular and Molecular Biology, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
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.
Insights
Extracellular vesicles from Paracoccidioides brasiliensis promote M1 macrophage polarization, enhancing the host immune response against fungal infections. These EVs modulate immune cells, impacting the host-pathogen relationship.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Extracellular vesicles (EVs) carry diverse molecules and can influence host-pathogen interactions.
- Paracoccidioides brasiliensis is a fungus causing paracoccidioidomycosis, a significant human mycosis.
- The immunomodulatory effects of P. brasiliensis EVs on host immune cells remain largely unexplored.
Purpose of the Study:
- To investigate the impact of P. brasiliensis EVs on murine macrophage polarization and function.
- To determine if P. brasiliensis EVs can alter the balance between M1 and M2 macrophage phenotypes.
Main Methods:
- Murine macrophages were treated with P. brasiliensis EVs.
- Macrophage polarization markers (iNOS, Arginase-1, Ym-1, FIZZ-1) were analyzed via transcription.
- Proinflammatory mediator production and fungicidal activity were assessed.
Main Results:
- P. brasiliensis EVs induced proinflammatory mediator production in a dose-dependent manner.
- EVs promoted M1 macrophage polarization by upregulating iNOS and downregulating M2 markers.
- EVs reverted M2 polarization to M1 and enhanced macrophage fungicidal activity against P. brasiliensis.
Conclusions:
- P. brasiliensis EVs modulate the innate immune response by inducing M1 macrophage polarization.
- EV-induced M1 polarization enhances macrophage fungicidal activity, potentially impacting P. brasiliensis infection outcomes.
- EVs play a role in the complex interplay between P. brasiliensis and host immune cells.
