title: Constitutive gene expression in monocytes from chronic HIV-1 infection overlaps with acute Toll-like receptor induced monocyte activation profiles.
abstract: 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.
authors: The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
authors: Bethsebah
authors: B
authors: Gekonge
authors: Malavika S
authors: MS
authors: Giri
authors: Andrew V
authors: AV
authors: Kossenkov
authors: Michael
authors: M
authors: Nebozyhn
authors: Malik
authors: M
authors: Yousef
authors: Karam
authors: K
authors: Mounzer
authors: Louise
authors: L
authors: Showe
authors: Luis J
authors: LJ
authors: Montaner
mesh_terms: D000328:Adult; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D025341:Principal Component Analysis; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors