biostudies-literature00550Cronemberger-Andrade ANIMHD NIH HHS99https://www.ebi.ac.uk/biostudies/studies/S-EPMC7098991biostudies-literatureUnknown10Extracellular vesicles (EVs) shed by trypomastigote forms of <i>Trypanosoma cruzi</i> have the ability to interact with host tissues, increase invasion, and modulate the host innate response. In this study, EVs shed from <i>T. cruzi or T.cruzi</i>-infected macrophages were investigated as immunomodulatory agents during the initial steps of infection. Initially, by scanning electron microscopy and nanoparticle tracking analysis, we determined that <i>T. cruzi</i>-infected macrophages release higher numbers of EVs (50-300 nm) as compared to non-infected cells. Using Toll-like-receptor 2 (TLR2)-transfected CHO cells, we observed that pre-incubation of these host cells with parasite-derived EVs led to an increase in the percentage of infected cells. In addition, EVs from parasite or <i>T.cruzi</i>-infected macrophages or not were able to elicit translocation of NF-κB by interacting with TLR2, and as a consequence, to alter the EVs the gene expression of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), and STAT-1 and STAT-3 signaling pathways. By proteomic analysis, we observed highly significant changes in the protein composition between non-infected and infected host cell-derived EVs. Thus, we observed the potential of EVs derived from <i>T. cruzi</i> during infection to maintain the inflammatory response in the host.Frontiers in cellular and infection microbiology<i>Trypanosoma cruzi</i>-Infected Human Macrophages Shed Proinflammatory Extracellular Vesicles That Enhance Host-Cell Invasion via Toll-Like Receptor 2.PMC7098991G12 MD007592Ofir-Birin YAlmeida ICRegev-Rudzki NXander PSoares RPEllis CCPessoa NLCampos MAGrajeda BTorrecilhas ACCronemberger-Andrade A55false<i>Trypanosoma cruzi</i>-Infected Human Macrophages Shed Proinflammatory Extracellular Vesicles That Enhance Host-Cell Invasion via Toll-Like Receptor 2.Extracellular vesicles (EVs) shed by trypomastigote forms of <i>Trypanosoma cruzi</i> have the ability to interact with host tissues, increase invasion, and modulate the host innate response. In this study, EVs shed from <i>T. cruzi or T.cruzi</i>-infected macrophages were investigated as immunomodulatory agents during the initial steps of infection. Initially, by scanning electron microscopy and nanoparticle tracking analysis, we determined that <i>T. cruzi</i>-infected macrophages release higher numbers of EVs (50-300 nm) as compared to non-infected cells. Using Toll-like-receptor 2 (TLR2)-transfected CHO cells, we observed that pre-incubation of these host cells with parasite-derived EVs led to an increase in the percentage of infected cells. In addition, EVs from parasite or <i>T.cruzi</i>-infected macrophages or not were able to elicit translocation of NF-κB by interacting with TLR2, and as a consequence, to alter the EVs the gene expression of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), and STAT-1 and STAT-3 signaling pathways. By proteomic analysis, we observed highly significant changes in the protein composition between non-infected and infected host cell-derived EVs. Thus, we observed the potential of EVs derived from <i>T. cruzi</i> during infection to maintain the inflammatory response in the host.2020-01-01T00:00:00Z20202024-02-15T22:02:31.449Z2020-05-22T16:17:15ZS-EPMC70989913226616110.3389/fcimb.2020.00099