PMID- 36467728 OWN - NLM STAT- MEDLINE DCOM- 20221206 LR - 20221206 IS - 2235-2988 (Electronic) IS - 2235-2988 (Linking) VI - 12 DP - 2022 TI - Extracellular vesicles from Trypanosoma cruzi-dendritic cell interaction show modulatory properties and confer resistance to lethal infection as a cell-free based therapy strategy. PG - 980817 LID - 10.3389/fcimb.2022.980817 [doi] LID - 980817 AB - Extracellular vesicles (EVs) include a heterogeneous group of particles. Microvesicles, apoptotic bodies and exosomes are the most characterized vesicles. They can be distinguished by their size, morphology, origin and molecular composition. To date, increasing studies demonstrate that EVs mediate intercellular communication. EVs reach considerable interest in the scientific community due to their role in diverse processes including antigen-presentation, stimulation of anti-tumoral immune responses, tolerogenic or inflammatory effects. In pathogens, EV shedding is well described in fungi, bacteria, protozoan and helminths parasites. For Trypanosoma cruzi EV liberation and protein composition was previously described. Dendritic cells (DCs), among other cells, are key players promoting the immune response against pathogens and also maintaining self-tolerance. In previous reports we have demonstrate that T. cruzi downregulates DCs immunogenicity in vitro and in vivo. Here we analyze EVs from the in vitro interaction between blood circulating trypomastigotes (Tp) and bone-marrow-derived DCs. We found that Tp incremented the number and the size of EVs in cultures with DCs. EVs displayed some exosome markers and intracellular RNA. Protein analysis demonstrated that the parasite changes the DC protein-EV profile. We observed that EVs from the interaction of Tp-DCs were easily captured by unstimulated-DCs in comparison with EVs from DCs cultured without the parasite, and also modified the activation status of LPS-stimulated DCs. Noteworthy, we found protection in animals treated with EVs-DCs+Tp and challenged with T. cruzi lethal infection. Our goal is to go deep into the molecular characterization of EVs from the DCs-Tp interaction, in order to identify mediators for therapeutic purposes. CI - Copyright (c) 2022 Gutierrez, Ancarola, Volpato-Rossi, Marcilla, Ramirez, Rosenzvit, Cucher and Poncini. FAU - Gutierrez, Brenda Celeste AU - Gutierrez BC AD - Instituto de Investigaciones en Microbiologia y Parasitologia Medicas (IMPaM), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina. FAU - Ancarola, Maria Eugenia AU - Ancarola ME AD - Instituto de Investigaciones en Microbiologia y Parasitologia Medicas (IMPaM), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina. FAU - Volpato-Rossi, Izadora AU - Volpato-Rossi I AD - Programa de Pos-graduacao em Biologia Celular e Molecular, Universidade Federal do Parana, Curitiba, Parana, Brazil. AD - Instituto Carlos Chagas - Fiocruz Parana, Curitiba, Parana, Brazil. FAU - Marcilla, Antonio AU - Marcilla A AD - Departamento de Farmacia y Tecnologia Farmaceutica y Parasitologia, Universitat de Valencia, Valencia, Spain. FAU - Ramirez, Marcel Ivan AU - Ramirez MI AD - Programa de Pos-graduacao em Biologia Celular e Molecular, Universidade Federal do Parana, Curitiba, Parana, Brazil. AD - Instituto Carlos Chagas - Fiocruz Parana, Curitiba, Parana, Brazil. FAU - Rosenzvit, Mara Cecilia AU - Rosenzvit MC AD - Instituto de Investigaciones en Microbiologia y Parasitologia Medicas (IMPaM), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina. FAU - Cucher, Marcela AU - Cucher M AD - Instituto de Investigaciones en Microbiologia y Parasitologia Medicas (IMPaM), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina. FAU - Poncini, Carolina Veronica AU - Poncini CV AD - Instituto de Investigaciones en Microbiologia y Parasitologia Medicas (IMPaM), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina. AD - Departamento de Microbiologia, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221116 PL - Switzerland TA - Front Cell Infect Microbiol JT - Frontiers in cellular and infection microbiology JID - 101585359 SB - IM MH - Animals MH - *Trypanosoma cruzi MH - *Extracellular Vesicles MH - Cell Communication MH - *Chagas Disease/therapy MH - *Exosomes PMC - PMC9710384 OTO - NOTNLM OT - T. cruzi OT - cell free therapy OT - dendric cells (DCs) OT - dendritic cells OT - extracellular vesicles (EVs) OT - immunotherapy COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/12/06 06:00 MHDA- 2022/12/07 06:00 PMCR- 2022/01/01 CRDT- 2022/12/05 04:31 PHST- 2022/06/28 00:00 [received] PHST- 2022/10/20 00:00 [accepted] PHST- 2022/12/05 04:31 [entrez] PHST- 2022/12/06 06:00 [pubmed] PHST- 2022/12/07 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fcimb.2022.980817 [doi] PST - epublish SO - Front Cell Infect Microbiol. 2022 Nov 16;12:980817. doi: 10.3389/fcimb.2022.980817. eCollection 2022.