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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Extracellular Vesicles Released by Leishmania (Leishmania) amazonensis Promote Disease Progression and Induce the Production of Different Cytokines in Macrophages and B-1 Cells

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Costa Barbosa, Fernanda Marins [1] ; Dupin, Talita Vieira [1] ; Toledo, Mayte dos Santos [1] ; dos Campos Reis, Natasha Ferraz [1] ; Ribeiro, Kleber [1] ; Cronemberger-Andrade, Andre [1] ; Rugani, Jeronimo Nunes [2] ; Pizarro De Lorenzo, Beatriz Helena [3] ; Novaes e Brito, Ronni Romulo [3] ; Soares, Rodrigo Pedro [2] ; Torrecilhas, Ana Claudia [1] ; Xander, Patricia [1]
Total Authors: 12
Affiliation:
[1] Univ Fed Sao Paulo, Lab Imunol Celular & Bioquim Fungos & Protozoario, Dept Ciencias Farmaceut, Campus Diadema, Diadema - Brazil
[2] Fiocruz MS, Inst Rene Rachou, Belo Horizonte, MG - Brazil
[3] Ctr Univ Sao Camilo, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: FRONTIERS IN MICROBIOLOGY; v. 9, DEC 21 2018.
Web of Science Citations: 2
Abstract

The extracellular vesicles (EVs) released by Leishmania can contribute to the establishment of infection and host immunomodulation. In this study, we characterized the shedding of EVs from Leishmania (Leishmania) amazonensis promastigotes. This species is the causative agent of cutaneous leishmaniasis, and its role during interactions with bone marrow-derived macrophages (BMDMs) and peritoneal B-1 cells was evaluated. Leishmania amazonensis promastigotes cultivated in vitro at different times and temperatures spontaneously released EVs. EVs were purified using size-exclusion chromatography (SEC) and quantitated by nanoparticle tracking analysis (NTA). NTA revealed that the average size of the EVs was approximately 180 nm, with concentrations ranging from 1.8 x 10(8) to 2.4 x 10(9) vesicles/mL. In addition, the presence of LPG and GP63 were detected in EVs obtained at different temperatures. NaNe BMDMs stimulated with EVs exhibited increased IL-10 and IL-6 expression. However, incubating B-1 cells with parasite EVs did not stimulate IL-10 expression but led to an increase in the expression of IL-6 and TNF alpha. After 7 weeks post-infection, animals infected with L. amazonensis promastigotes in the presence of parasite EVs had significant higher parasite load and a polarization to Th2 response, as compared to the group infected with the parasite alone. This work demonstrated that EVs isolated from L. amazonensis promastigotes were able to stimulate macrophages and B-1 cells to express different types of cytokines. Moreover, the immunomodulatory properties of EVs probably contributed to an increase in parasite burden in mice. These findings suggest that the functionality of L. amazonensis EVs on immune system favor of parasite survival and disease progression. (AU)

FAPESP's process: 16/17245-4 - Study of the effects of extracellular vesicles released by Leishmania amazonensis promastigotes on macrophages response and disease progression
Grantee:Patricia Xander Batista
Support Opportunities: Regular Research Grants