Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy

Abstract Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients...

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Autores principales:	Sukrutha Chettimada, David R. Lorenz, Vikas Misra, Simon T. Dillon, R. Keith Reeves, Cordelia Manickam, Susan Morgello, Gregory D. Kirk, Shruti H. Mehta, Dana Gabuzda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b897ba8872bc48c9b7875ebc758d9ce5
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spelling	oai:doaj.org-article:b897ba8872bc48c9b7875ebc758d9ce52021-12-02T12:33:00ZExosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy10.1038/s41598-018-25515-42045-2322https://doaj.org/article/b897ba8872bc48c9b7875ebc758d9ce52018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25515-4https://doaj.org/toc/2045-2322Abstract Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics. Plasma exosomes were increased in HIV-positive subjects compared to controls, and correlated with increased oxidative stress markers (cystine, oxidized cys-gly) and decreased PUFA (DHA, EPA, DPA). Untargeted proteomics detected markers of exosomes (CD9, CD63, CD81), immune activation (CD14, CRP, HLA-A, HLA-B), oxidative stress (CAT, PRDX1, PRDX2, TXN), and Notch4 in plasma exosomes. Exosomal Notch4 was increased in HIV-positive subjects versus controls and correlated with immune activation markers. Treatment of THP-1 monocytic cells with patient-derived exosomes induced expression of genes related to interferon responses and immune activation. These results suggest that exosomes in ART-treated HIV patients carry proteins related to immune activation and oxidative stress, have immunomodulatory effects on myeloid cells, and may have pro-inflammatory and redox effects during pathogenesis.Sukrutha ChettimadaDavid R. LorenzVikas MisraSimon T. DillonR. Keith ReevesCordelia ManickamSusan MorgelloGregory D. KirkShruti H. MehtaDana GabuzdaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-16 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sukrutha Chettimada David R. Lorenz Vikas Misra Simon T. Dillon R. Keith Reeves Cordelia Manickam Susan Morgello Gregory D. Kirk Shruti H. Mehta Dana Gabuzda Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy
description	Abstract Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics. Plasma exosomes were increased in HIV-positive subjects compared to controls, and correlated with increased oxidative stress markers (cystine, oxidized cys-gly) and decreased PUFA (DHA, EPA, DPA). Untargeted proteomics detected markers of exosomes (CD9, CD63, CD81), immune activation (CD14, CRP, HLA-A, HLA-B), oxidative stress (CAT, PRDX1, PRDX2, TXN), and Notch4 in plasma exosomes. Exosomal Notch4 was increased in HIV-positive subjects versus controls and correlated with immune activation markers. Treatment of THP-1 monocytic cells with patient-derived exosomes induced expression of genes related to interferon responses and immune activation. These results suggest that exosomes in ART-treated HIV patients carry proteins related to immune activation and oxidative stress, have immunomodulatory effects on myeloid cells, and may have pro-inflammatory and redox effects during pathogenesis.
format	article
author	Sukrutha Chettimada David R. Lorenz Vikas Misra Simon T. Dillon R. Keith Reeves Cordelia Manickam Susan Morgello Gregory D. Kirk Shruti H. Mehta Dana Gabuzda
author_facet	Sukrutha Chettimada David R. Lorenz Vikas Misra Simon T. Dillon R. Keith Reeves Cordelia Manickam Susan Morgello Gregory D. Kirk Shruti H. Mehta Dana Gabuzda
author_sort	Sukrutha Chettimada
title	Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy
title_short	Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy
title_full	Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy
title_fullStr	Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy
title_full_unstemmed	Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy
title_sort	exosome markers associated with immune activation and oxidative stress in hiv patients on antiretroviral therapy
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/b897ba8872bc48c9b7875ebc758d9ce5
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Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy

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