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The Impact of HIV Co-Infection on the Genomic Response to Sepsis

HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection...

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Autores principales: Huson, Michaëla A. M., Scicluna, Brendon P., van Vught, Lonneke A., Wiewel, Maryse A., Hoogendijk, Arie J., Cremer, Olaf L., Bonten, Marc J. M., Schultz, Marcus J., Franitza, Marek, Toliat, Mohammad R., Nürnberg, Peter, Grobusch, Martin P., van der Poll, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752296/
https://www.ncbi.nlm.nih.gov/pubmed/26871709
http://dx.doi.org/10.1371/journal.pone.0148955
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author Huson, Michaëla A. M.
Scicluna, Brendon P.
van Vught, Lonneke A.
Wiewel, Maryse A.
Hoogendijk, Arie J.
Cremer, Olaf L.
Bonten, Marc J. M.
Schultz, Marcus J.
Franitza, Marek
Toliat, Mohammad R.
Nürnberg, Peter
Grobusch, Martin P.
van der Poll, Tom
author_facet Huson, Michaëla A. M.
Scicluna, Brendon P.
van Vught, Lonneke A.
Wiewel, Maryse A.
Hoogendijk, Arie J.
Cremer, Olaf L.
Bonten, Marc J. M.
Schultz, Marcus J.
Franitza, Marek
Toliat, Mohammad R.
Nürnberg, Peter
Grobusch, Martin P.
van der Poll, Tom
author_sort Huson, Michaëla A. M.
collection PubMed
description HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis.
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spelling pubmed-47522962016-02-26 The Impact of HIV Co-Infection on the Genomic Response to Sepsis Huson, Michaëla A. M. Scicluna, Brendon P. van Vught, Lonneke A. Wiewel, Maryse A. Hoogendijk, Arie J. Cremer, Olaf L. Bonten, Marc J. M. Schultz, Marcus J. Franitza, Marek Toliat, Mohammad R. Nürnberg, Peter Grobusch, Martin P. van der Poll, Tom PLoS One Research Article HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis. Public Library of Science 2016-02-12 /pmc/articles/PMC4752296/ /pubmed/26871709 http://dx.doi.org/10.1371/journal.pone.0148955 Text en © 2016 Huson 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
Huson, Michaëla A. M.
Scicluna, Brendon P.
van Vught, Lonneke A.
Wiewel, Maryse A.
Hoogendijk, Arie J.
Cremer, Olaf L.
Bonten, Marc J. M.
Schultz, Marcus J.
Franitza, Marek
Toliat, Mohammad R.
Nürnberg, Peter
Grobusch, Martin P.
van der Poll, Tom
The Impact of HIV Co-Infection on the Genomic Response to Sepsis
title The Impact of HIV Co-Infection on the Genomic Response to Sepsis
title_full The Impact of HIV Co-Infection on the Genomic Response to Sepsis
title_fullStr The Impact of HIV Co-Infection on the Genomic Response to Sepsis
title_full_unstemmed The Impact of HIV Co-Infection on the Genomic Response to Sepsis
title_short The Impact of HIV Co-Infection on the Genomic Response to Sepsis
title_sort impact of hiv co-infection on the genomic response to sepsis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752296/
https://www.ncbi.nlm.nih.gov/pubmed/26871709
http://dx.doi.org/10.1371/journal.pone.0148955
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