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Constitutive Gene Expression in Monocytes from Chronic HIV-1 Infection Overlaps with Acute Toll-Like Receptor Induced Monocyte Activation Profiles
Open accessAbstract
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.
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Metadata
- Authors
- Gekonge, B., Giri, M. S., Kossenkov, A. V., Nebozyhn, M., Yousef, M., Mounzer, K., Showe, L., & Montaner, L. J.
- Affiliations
- The Wistar Institute (US)
- Corresponding author
- Montaner, Luis J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-07-18
- Volume
- 7
- Issue
- 7
- Pages
- e41153
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3399809
- OpenAlex
- W2033693429
- Cited by
- 21
- References
- 36
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 1
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Pennsylvania Department of Health
- Philadelphia Foundation
- National Institutes of Health (A1047760, CA010815)
- U.S. Public Health Service (A1047760)
- National Cancer Institute (CA010815, P30CA010815)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Infectious Diseases › HIV-related health complications and treatments
- Keywords
- chronic HIV-1 infection, monocytes, Toll-like receptors, TLR2, constitutive expression, monocyte activation, systemic immune activation, ERK signaling, NF-κB signaling, p53, inflammatory gene expression
- MeSH terms
- Adult, Female, Flow Cytometry, Gene Expression Regulation, Humans, Inflammation, Macrophages, Male, Middle Aged, Models, Biological, Monocytes, Signal Transduction, HIV-1, HIV Infections, Principal Component Analysis, Toll-Like Receptors, Toll-Like Receptor 2
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