Constitutive Gene Expression in Monocytes from Chronic HIV-1 Infection Overlaps with Acute Toll-Like Receptor Induced Monocyte Activation Profiles
| Autor: | Malavika S. Giri, Karam Mounzer, Michael Nebozyhn, Bethsebah Gekonge, Andrew V. Kossenkov, Luis J. Montaner, Malik Yousef, Louise C. Showe |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Gene Expression lcsh:Medicine HIV Infections Signal transduction ERK signaling cascade Monocytes Molecular cell biology 0302 clinical medicine Immunodeficiency Viruses Gene expression Genome Databases Genetics of the Immune System lcsh:Science Regulation of gene expression Principal Component Analysis 0303 health sciences Toll-like receptor Multidisciplinary Toll-Like Receptors Signaling cascades Genomics Middle Aged Flow Cytometry 3. Good health medicine.anatomical_structure Female Tumor necrosis factor alpha Research Article Adult MAPK signaling cascades Immune Cells Immunology Immunopathology Biology Models Biological Microbiology Molecular Genetics Immunomodulation 03 medical and health sciences Virology medicine Humans 030304 developmental biology Inflammation Macrophages Monocyte lcsh:R Computational Biology Gene signature Toll-Like Receptor 2 TLR2 Gene Expression Regulation HIV-1 lcsh:Q Genome Expression Analysis Ex vivo 030215 immunology |
| Zdroj: | PLoS ONE, Vol 7, Iss 7, p e41153 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0041153 |
| Popis: | Elevated TLR expression/signalling in monocyte/macrophages has been shown to mediate systemic immune activation, a hallmark of progressive HIV-1 infection. Here we show, via differential gene expression comparisons, the presence of a constitutive in vivo TLR-like gene activation signature in steady-state circulating monocytes from chronically HIV-1 infected subjects. The TLR2-like gene signature was defined as an 82 gene subset of the 376 genes constitutively modulated in in vivo HIV-1 monocytes, based on their overlap with de novo TLR2-induced genes in uninfected subjects’ monocytes following acute ex vivo stimulation with Staphylococcus Aureus Cowan (SAC). Additional comparison of in vivo gene networks with available datasets from acute TLR activations in M/M expanded the overlap to 151-gene concordance among the 376 differential genes with emphasis on ERK/MAPK, TNF/IL6 (NFκB) and p53 gene networks. TLR2 stimulation of monocytes from HIV-1 infected subjects resulted in further upregulation of inflammatory genes indicative of a sustained transcriptional potential upon stimulation. In summary, our data support the presence of a sustained TLR-like gene activation profile in circulating monocyte from steady-state viremia in HIV-1 infected subjects. |
| Databáze: | OpenAIRE |
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