Universität zu Köln

Huson, Michaela 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., Nuernberg, Peter, Grobusch, Martin P. and van der Poll, Tom (2016). The Impact of HIV Co-Infection on the Genomic Response to Sepsis. PLoS One, 11 (2). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Huson, Michaela A. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scicluna, Brendon P. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Vught, Lonneke A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiewel, Maryse A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoogendijk, Arie J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cremer, Olaf L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bonten, Marc J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultz, Marcus J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Franitza, Marek UNSPECIFIED UNSPECIFIED UNSPECIFIED Toliat, Mohammad R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Grobusch, Martin P. UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Poll, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-284608
DOI:	10.1371/journal.pone.0148955
Journal or Publication Title:	PLoS One
Volume:	11
Number:	2
Date:	2016
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; HOST RESPONSE; SEPTIC SHOCK; INFECTIONS; CARE; DEFINITIONS; BIOMARKER Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28460