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Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation

BACKGROUND: Cellular immunometabolism among people living with HIV (PLWH) on antiretroviral therapy (ART) remains under investigated. We assessed the relationships between mitochondrial oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) and blood parameters associated w...

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Autores principales: Gangcuangco, Louie Mar A., Mitchell, Brooks I., Siriwardhana, Chathura, Kohorn, Lindsay B., Chew, Glen M., Bowler, Scott, Kallianpur, Kalpana J., Chow, Dominic C., Ndhlovu, Lishomwa C., Gerschenson, Mariana, Shikuma, Cecilia M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192478/
https://www.ncbi.nlm.nih.gov/pubmed/32353005
http://dx.doi.org/10.1371/journal.pone.0231761
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author Gangcuangco, Louie Mar A.
Mitchell, Brooks I.
Siriwardhana, Chathura
Kohorn, Lindsay B.
Chew, Glen M.
Bowler, Scott
Kallianpur, Kalpana J.
Chow, Dominic C.
Ndhlovu, Lishomwa C.
Gerschenson, Mariana
Shikuma, Cecilia M.
author_facet Gangcuangco, Louie Mar A.
Mitchell, Brooks I.
Siriwardhana, Chathura
Kohorn, Lindsay B.
Chew, Glen M.
Bowler, Scott
Kallianpur, Kalpana J.
Chow, Dominic C.
Ndhlovu, Lishomwa C.
Gerschenson, Mariana
Shikuma, Cecilia M.
author_sort Gangcuangco, Louie Mar A.
collection PubMed
description BACKGROUND: Cellular immunometabolism among people living with HIV (PLWH) on antiretroviral therapy (ART) remains under investigated. We assessed the relationships between mitochondrial oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) and blood parameters associated with HIV immune dysregulation. METHODS: PLWH ≥40 years old and on stable ART ≥3 months were enrolled (N = 149). OXPHOS complex I (CI, NADH dehydrogenase) and complex IV (CIV, cytochrome c oxidase) protein levels in PBMCs were quantified using immunoassays. Monocyte subsets and markers of T-cell activation, senescence, and exhaustion were measured on PBMC by flow cytometry. Plasma inflammatory mediators were quantified using a multiplex assay. HIV-uninfected group (N = 44) of similar age, gender, and ethnicity had available OXPHOS levels. RESULTS: PLWH had a median age of 51 years. Majority were male (88.6%), Caucasian (57.7%), and with undetectable plasma HIV RNA <50 copies/mL (84.6%). Median CI level was lower in PLWH compared with the HIV-seronegative group (65.5 vs 155.0 optical density/μg protein x 10(3), p <0.0001). There was no significant difference in median CIV levels. Lower OXPHOS levels correlated with lower CD4% and CD4/CD8 ratio. On multivariable linear regression adjusted for age, current use of zidovudine/didanosine, and HIV RNA (detectable versus undetectable), lower OXPHOS levels were significantly associated with higher MPO, SAA, SAP, and sVCAM, and higher frequencies of intermediate (CD14(++)CD16(+)) monocytes and TIGIT+TIM3+ CD4 T-cell (p<0.01). CONCLUSION: CI PBMC protein levels were decreased in PLWH on ART. Decreased OXPHOS correlated with disease severity and inflammation. Further studies on the relationship between immunometabolism and immune dysregulation in HIV are warranted.
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spelling pubmed-71924782020-05-11 Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation Gangcuangco, Louie Mar A. Mitchell, Brooks I. Siriwardhana, Chathura Kohorn, Lindsay B. Chew, Glen M. Bowler, Scott Kallianpur, Kalpana J. Chow, Dominic C. Ndhlovu, Lishomwa C. Gerschenson, Mariana Shikuma, Cecilia M. PLoS One Research Article BACKGROUND: Cellular immunometabolism among people living with HIV (PLWH) on antiretroviral therapy (ART) remains under investigated. We assessed the relationships between mitochondrial oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) and blood parameters associated with HIV immune dysregulation. METHODS: PLWH ≥40 years old and on stable ART ≥3 months were enrolled (N = 149). OXPHOS complex I (CI, NADH dehydrogenase) and complex IV (CIV, cytochrome c oxidase) protein levels in PBMCs were quantified using immunoassays. Monocyte subsets and markers of T-cell activation, senescence, and exhaustion were measured on PBMC by flow cytometry. Plasma inflammatory mediators were quantified using a multiplex assay. HIV-uninfected group (N = 44) of similar age, gender, and ethnicity had available OXPHOS levels. RESULTS: PLWH had a median age of 51 years. Majority were male (88.6%), Caucasian (57.7%), and with undetectable plasma HIV RNA <50 copies/mL (84.6%). Median CI level was lower in PLWH compared with the HIV-seronegative group (65.5 vs 155.0 optical density/μg protein x 10(3), p <0.0001). There was no significant difference in median CIV levels. Lower OXPHOS levels correlated with lower CD4% and CD4/CD8 ratio. On multivariable linear regression adjusted for age, current use of zidovudine/didanosine, and HIV RNA (detectable versus undetectable), lower OXPHOS levels were significantly associated with higher MPO, SAA, SAP, and sVCAM, and higher frequencies of intermediate (CD14(++)CD16(+)) monocytes and TIGIT+TIM3+ CD4 T-cell (p<0.01). CONCLUSION: CI PBMC protein levels were decreased in PLWH on ART. Decreased OXPHOS correlated with disease severity and inflammation. Further studies on the relationship between immunometabolism and immune dysregulation in HIV are warranted. Public Library of Science 2020-04-30 /pmc/articles/PMC7192478/ /pubmed/32353005 http://dx.doi.org/10.1371/journal.pone.0231761 Text en © 2020 Gangcuangco et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gangcuangco, Louie Mar A.
Mitchell, Brooks I.
Siriwardhana, Chathura
Kohorn, Lindsay B.
Chew, Glen M.
Bowler, Scott
Kallianpur, Kalpana J.
Chow, Dominic C.
Ndhlovu, Lishomwa C.
Gerschenson, Mariana
Shikuma, Cecilia M.
Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation
title Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation
title_full Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation
title_fullStr Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation
title_full_unstemmed Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation
title_short Mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic HIV and correlates with immune dysregulation
title_sort mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells is decreased in chronic hiv and correlates with immune dysregulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192478/
https://www.ncbi.nlm.nih.gov/pubmed/32353005
http://dx.doi.org/10.1371/journal.pone.0231761
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