Abstract
All extracellular forms of Trypanosoma cruzi, the causative agent of Chagas disease, release extracellular vesicles (EVs) containing major surface molecules of the parasite. EV release depends on several mechanisms (internal and external). However, most of the environmental conditions affecting this phenomenon are still unknown. In this work, we evaluated EV release under different stress conditions and their ability to be internalized by the parasites. In addition, we investigated whether the release conditions would affect their immunomodulatory properties in preactivated bone marrow-derived macrophages (BMDM). Sodium azide and methyl-cyclo-β-dextrin (CDB) reduced EV release, indicating that this phenomenon relies on membrane organization. EV release was increased at low temperatures (4°C) and acidic conditions (pH 5.0). Under this pH, trypomastigotes differentiated into amastigotes. EVs are rapidly liberated and reabsorbed by the trypomastigotes in a concentration-dependent manner. Nitrosative stress caused by sodium nitrite in acid medium or S-nitrosoglutathione also stimulated the secretion of EVs. EVs released under all stress conditions also maintained their proinflammatory activity and increased the expression of iNOS, Arg 1, IL-12, and IL-23 genes in IFN-γ and LPS preactivated BMDM. In conclusion, our results suggest a budding mechanism of release, dependent on the membrane structure and parasite integrity. Stress conditions did not affect functional properties of EVs during interaction with host cells. EV release variations under stress conditions may be a physiological response against environmental changes.
Highlights
The flagellated protozoan Trypanosoma cruzi is the etiological agent of Chagas disease, affecting 8 million people worldwide
We evaluated if T. cruzi extracellular vesicles (EVs) released under stress conditions were functionally affected during interaction with bone marrow-derived macrophages
EVs were collected after 30 minutes of parasite resuspension in the serum-free DMEM containing 5% glucose
Summary
The flagellated protozoan Trypanosoma cruzi is the etiological agent of Chagas disease, affecting 8 million people worldwide. 100 million people are at risk of infection, causing about 2,000 deaths per year. These circumstances make this disease a serious health problem [1, 2]. Trypomastigotes derived from infected mammalian cell cultures release extracellular vesicles (EVs) in the culture medium. They express major protozoan surface molecules [2], including mucin-like glycoproteins, glycosylphosphatidyl inositol phospholipids (GIPLs), and members of the gp85/trans-sialidase (TS) superfamily of glycoproteins [3]
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