PMID- 30627118 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 9 DP - 2018 TI - Extracellular Vesicles Released by Leishmania (Leishmania) amazonensis Promote Disease Progression and Induce the Production of Different Cytokines in Macrophages and B-1 Cells. PG - 3056 LID - 10.3389/fmicb.2018.03056 [doi] LID - 3056 AB - 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. Naive 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 TNFalpha. 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. FAU - Barbosa, Fernanda Marins Costa AU - Barbosa FMC AD - Laboratorio de Imunologia Celular e Bioquimica de Fungos e Protozoarios, Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo - Campus Diadema, Diadema, Brazil. FAU - Dupin, Talita Vieira AU - Dupin TV AD - Laboratorio de Imunologia Celular e Bioquimica de Fungos e Protozoarios, Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo - Campus Diadema, Diadema, Brazil. FAU - Toledo, Mayte Dos Santos AU - Toledo MDS AD - Laboratorio de Imunologia Celular e Bioquimica de Fungos e Protozoarios, Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo - Campus Diadema, Diadema, Brazil. FAU - Reis, Natasha Ferraz Dos Campos AU - Reis NFDC AD - Laboratorio de Imunologia Celular e Bioquimica de Fungos e Protozoarios, Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo - Campus Diadema, Diadema, Brazil. FAU - Ribeiro, Kleber AU - Ribeiro K AD - Laboratorio de Imunologia Celular e Bioquimica de Fungos e Protozoarios, Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo - Campus Diadema, Diadema, Brazil. FAU - Cronemberger-Andrade, Andre AU - Cronemberger-Andrade A AD - Laboratorio de Imunologia Celular e Bioquimica de Fungos e Protozoarios, Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo - Campus Diadema, Diadema, Brazil. FAU - Rugani, Jeronimo Nunes AU - Rugani JN AD - Instituto Rene Rachou/FIOCRUZ, Belo Horizonte, Brazil. FAU - De Lorenzo, Beatriz Helena Pizarro AU - De Lorenzo BHP AD - Centro Universitario Sao Camilo, Sao Paulo, Brazil. FAU - Novaes E Brito, Ronni Romulo AU - Novaes E Brito RR AD - Centro Universitario Sao Camilo, Sao Paulo, Brazil. FAU - Soares, Rodrigo Pedro AU - Soares RP AD - Instituto Rene Rachou/FIOCRUZ, Belo Horizonte, Brazil. FAU - Torrecilhas, Ana Claudia AU - Torrecilhas AC AD - Laboratorio de Imunologia Celular e Bioquimica de Fungos e Protozoarios, Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo - Campus Diadema, Diadema, Brazil. FAU - Xander, Patricia AU - Xander P AD - Laboratorio de Imunologia Celular e Bioquimica de Fungos e Protozoarios, Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo - Campus Diadema, Diadema, Brazil. LA - eng PT - Journal Article DEP - 20181221 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC6309564 OTO - NOTNLM OT - B-1 cells OT - L. amazonensis OT - cytokines OT - extracellular vesicles OT - macrophages EDAT- 2019/01/11 06:00 MHDA- 2019/01/11 06:01 PMCR- 2018/12/21 CRDT- 2019/01/11 06:00 PHST- 2018/04/02 00:00 [received] PHST- 2018/11/27 00:00 [accepted] PHST- 2019/01/11 06:00 [entrez] PHST- 2019/01/11 06:00 [pubmed] PHST- 2019/01/11 06:01 [medline] PHST- 2018/12/21 00:00 [pmc-release] AID - 10.3389/fmicb.2018.03056 [doi] PST - epublish SO - Front Microbiol. 2018 Dec 21;9:3056. doi: 10.3389/fmicb.2018.03056. eCollection 2018.