Cerebrospinal Fluid-Derived Microvesicles from Sleeping Sickness Patients Alter Protein Expression in Human Astrocytes

Human African trypanosomiasis (HAT) caused by the extracellular protozoon Trypanosoma brucei, is a neglected tropical disease affecting the poorest communities in sub-Saharan Africa. HAT progresses from a hemolymphatic first stage (S1) to a meningo-encephalitic late stage (S2) when parasites reach the central nervous system, although the existence of an intermediate stage (Int.) has also been proposed. The pathophysiological mechanisms associated with the development of S2 encephalopathy are yet to be fully elucidated. In the present study, we used data independent acquisition mass spectrometry (DIA-MS) to investigate the potential pathogenic effects of microvesicles (MVs) derived from HAT patients’ cerebrospinal fluid (CSF). To assess potential biological properties of these MVs, immortalized human astrocytes were exposed, in vitro, to MVs enriched from S1, Int. or S2 CSF. DIA-MS analyses showed that S2 MVs induced, compared to Int. or S1 MVs, a stronger proteome modulation in astrocytes that resembled the one produced by IFN-γ, a key molecule in HAT pathogenesis. Our results indicate that HAT S2 CSF harbors MVs potentially involved in the mechanisms of pathology associated with HAT late stage. Such vesicles might thus represent a new player to consider in future functional studies.