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

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 thei...

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Autores principales: Chettimada, Sukrutha, Lorenz, David R., Misra, Vikas, Dillon, Simon T., Reeves, R. Keith, Manickam, Cordelia, Morgello, Susan, Kirk, Gregory D., Mehta, Shruti H., Gabuzda, Dana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940833/
https://www.ncbi.nlm.nih.gov/pubmed/29740045
http://dx.doi.org/10.1038/s41598-018-25515-4
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author Chettimada, Sukrutha
Lorenz, David R.
Misra, Vikas
Dillon, Simon T.
Reeves, R. Keith
Manickam, Cordelia
Morgello, Susan
Kirk, Gregory D.
Mehta, Shruti H.
Gabuzda, Dana
author_facet Chettimada, Sukrutha
Lorenz, David R.
Misra, Vikas
Dillon, Simon T.
Reeves, R. Keith
Manickam, Cordelia
Morgello, Susan
Kirk, Gregory D.
Mehta, Shruti H.
Gabuzda, Dana
author_sort Chettimada, Sukrutha
collection PubMed
description 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.
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spelling pubmed-59408332018-05-11 Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy Chettimada, Sukrutha Lorenz, David R. Misra, Vikas Dillon, Simon T. Reeves, R. Keith Manickam, Cordelia Morgello, Susan Kirk, Gregory D. Mehta, Shruti H. Gabuzda, Dana Sci Rep Article 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. Nature Publishing Group UK 2018-05-08 /pmc/articles/PMC5940833/ /pubmed/29740045 http://dx.doi.org/10.1038/s41598-018-25515-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chettimada, Sukrutha
Lorenz, David R.
Misra, Vikas
Dillon, Simon T.
Reeves, R. Keith
Manickam, Cordelia
Morgello, Susan
Kirk, Gregory D.
Mehta, Shruti H.
Gabuzda, Dana
Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940833/
https://www.ncbi.nlm.nih.gov/pubmed/29740045
http://dx.doi.org/10.1038/s41598-018-25515-4
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