Extracellular Vesicles in Chagas Disease (Infectious Disease)

Chagas disease, caused by the protozoa parasite Trypanosomacruzi, is a neglected tropical disease and a major public healthproblem affecting more than ۶ million people worldwide. Thediagnosis presents several limitations, the two available treatmentscause several side effects and present limited efficacyduring the chronic phase of the disease. In addition, there areno preventive vaccines or biomarkers of therapeutic responseor disease outcome. Trypomas tigote form and T. cruzi infectedcells release extracellular vesicles (EVs), which are involvedin cell-to-cell communication and can modulate the hos t immuneresponse. We have shown that vesicles released by infectiveforms of Trypanosoma cruzi modulate the inflammatoryresponse of macrophages through the activation of Toll ۲ receptor(TLR۲) involving signaling pathways of mitogen-activatedprotein kinases (MAPK). This induces the production of nitricoxide (NO) and the cytokines TNF-α, IL-۱۲ and IL-۶, whichcould explain increased inflammation and the progression ofdisease in experimental models, and eventually the progressionof human Chagas’ disease. We also found that this process severalamong different isolates of the parasite that produce differentpatterns of infection. Furthermore, the vesicles released bythe parasite are heterogeneous and different vesicle populationsact during the interaction with hos t cells. We characterize the differentpopulations released by trypomas tigotes forms of T. cruzi(Y s train) by Asymmetric flow field-flow fractionation (AF۴)and Nanoparticles tracking analysis (NTA) and characterizationand to evaluate their interaction with hos t cells, particularly humanmonocytes cells (THP-۱) and parasite. We also determinethe intracellular signaling pathways and the produced cytokinesin each case. In Conclusion, our results could help to better understand the mechanism by which the dis tinct populations ofvesicles released by the parasite acts on the communication andmodulation parasite-human hos t cells interaction.