Abstract
Extracellular vesicles (EVs) shed by trypomastigote forms of Trypanosoma cruzi have the ability to interact with host tissues, increase invasion, and modulate the host innate response. In this study, EVs shed from T. cruzi or T.cruzi-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 T. cruzi-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 T.cruzi-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 T. cruzi during infection to maintain the inflammatory response in the host.
Highlights
Research interest in extracellular vesicles (EVs) and their involvement in cell-cell, cell-pathogen or pathogen-pathogen communication and modulation processes in infectious and inflammatory diseases has continuously grown in recent years (Campos et al, 2010)
In this work, we evaluated whether EV shed by T. cruzi infected macrophage modulate inflammatory responses and if EVs from cell-derived trypomastigotes could modify the cell invasion and the signaling mechanisms involved in this process
Compared to uninfected macrophages and those incubated with EVs from trypomastigotes (EV-TY), infected macrophages released a larger number of vesicles
Summary
Research interest in extracellular vesicles (EVs) and their involvement in cell-cell, cell-pathogen (parasites, viruses, bacteria, and fungi) or pathogen-pathogen communication and modulation processes in infectious and inflammatory diseases has continuously grown in recent years (Campos et al, 2010). The study of EVs has mainly focused on the types of membrane vesicles secreted into the extracellular compartment isolated from different cells, tissues, and biofluids in healthy and pathological conditions. EVs may be divided into exosomes, microvesicles, and apoptotic bodies (Théry et al, 2018; Mathieu et al, 2019; Witwer and Théry, 2019). EVs are secreted by either prokaryotic or eukaryotic cells, extending their phenotype (Campos et al, 2010; Torrecilhas et al, 2012)
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