Taenia solium extracellular vesicles decrease reactive oxygen species production in human neutrophils by inhibiting myeloperoxidase activity.

Abstract

Taenia solium cysticerci are the etiological agents of neurocysticercosis, a leading cause of acquired epilepsy worldwide and a significant public health problem in endemic regions. The chronicity of the infection reflects a complex host-parasite interaction in which the parasite establishes long-term persistence through immunomodulatory mechanisms. In recent years, extracellular vesicles (EVs) have emerged as important mediators for some of these interactions. EVs are membrane-bound structures released by virtually every organism studied, which carry a diverse set of molecules that mediate intercellular communication. We isolated Taenia solium extracellular vesicles (TsEVs) from racemose cysticerci recovered from a patient, subsequently cultured in vitro, in order to characterize them by transmission electron microscopy, nanoparticle tracking analysis, and mass spectrometry-based proteomics. Effect of TsEVs on the production of reactive oxygen species (ROS) and myeloperoxidase (MPO) activity was evaluated in human neutrophils using fluorometric and colorimetric assays under basal and chemically stimulated conditions. Obtained TsEVs were under 200 nm in diameter. Proteomic analysis of four independent TsEV samples allowed identification of a core set of 336 proteins. Gene Ontology analysis of these vesicles was consistent with exosomes, as a number of exosome-associated marker proteins such as tetraspanins were identified. Proteins linked to immunomodulation and redox metabolism were also identified, suggesting a potential role in interactions with host cells. Finally, the effect of TsEVs on the respiratory burst of human neutrophils was evaluated, revealing a reduction in ROS production, primarily through inhibition of MPO activity, adding up evidence for the role of these vesicles in parasite's survival against the host immune response.