@article{fdi:010077407, title = {{C}erebrospinal fluid-derived microvesicles from sleeping sickness patients alter protein expression in human astrocytes}, author = {{D}ozio, {V}. and {L}ejon, {V}eerle and {N}goyi, {D}. {M}. and {B}ilscher, {P}. and {S}anchez, {J}. {C}. and {T}iberti, {N}.}, editor = {}, language = {{ENG}}, abstract = {{H}uman {A}frican trypanosomiasis ({HAT}) caused by the extracellular protozoon {T}rypanosoma brucei, is a neglected tropical disease affecting the poorest communities in sub-{S}aharan {A}frica. {HAT} progresses from a hemolymphatic first stage ({S}1) to a meningo-encephalitic late stage ({S}2) when parasites reach the central nervous system ({CNS}), although the existence of an intermediate stage ({I}nt.) has also been proposed. {T}he pathophysiological mechanisms associated with the development of {S}2 encephalopathy are yet to be fully elucidated. {H}ere we hypothesized that {HAT} progression toward {S}2 might be accompanied by an increased release of microvesicles ({MV}s), sub-micron elements (0.1-1 mu m) involved in inflammatory processes and in the determination of the outcome of infections. {W}e studied the morphology of {MV}s isolated from {HAT} cerebrospinal fluid ({CSF}) by transmission electron microscopy ({TEM}) and used flow cytometry to show that total-{MV}s and leukocyte derived-{CD}45(+) {MV}s are significantly increased in concentration in {S}2 patients' {CSF} compared to {S}1 and {I}nt. samples (n = 12 per group). {T}o assess potential biological properties of these {MV}s, immortalized human astrocytes were exposed, in vitro, to {MV}s enriched from {S}1, {I}nt. or {S}2 {CSF}. {D}ata-independent acquisition mass spectrometry analyses showed that {S}2 {MV}s induced, compared to {I}nt. or {S}1 {MV}s, a strong proteome modulation in astrocytes that resembled the one produced by {IFN}-gamma, a key molecule in {HAT} pathogenesis. {O}ur results indicate that {HAT} {S}2 {CSF} harbors {MV}s potentially involved in the mechanisms of pathology associated with {HAT} late stage. {S}uch vesicles might thus represent a new player to consider in future functional studies.}, keywords = {human {A}frican trypanosomiasis ; microvesicles ; cerebrospinal fluid ; {DIA}-{MS} ; astrocytes ; {AFRIQUE} {SUBSAHARIENNE}}, booktitle = {}, journal = {{F}rontiers in {C}ellular and {I}nfection {M}icrobiology}, volume = {9}, numero = {}, pages = {art. 391 [9 p.]}, ISSN = {2235-2988}, year = {2019}, DOI = {10.3389/fcimb.2019.00391}, URL = {https://www.documentation.ird.fr/hor/fdi:010077407}, }