Abstract
ObjectiveTo characterize the effect of HIV infection on IL-27-induced gene expression.DesignDuring HIV infection, cytokine expression and function become deregulated. IL-27 is an important modulator of inflammatory responses. Interestingly, IL-27 can inhibit HIV replication in T cells and monocytes, implicating IL-27 as a potential adjunct to anti-viral treatment. Our previous work demonstrated that circulating HIV may suppress IL-27 expression, therefore, this study, in continuation of our previous work, aimed to understand how HIV affects expression levels of the IL-27 receptor and downstream functions of IL-27.MethodsPeripheral blood mononuclear cells (PBMC) were isolated from whole blood of HIV negative and HIV positive (viremic) individuals to assess IL-27-induced gene expression by flow cytometry and ELISA. PBMC were also processed for monocyte enrichment to assess IL-27 receptor expression by flow cytometry and real-time PCR.ResultsExpression of the IL-27 receptor subunit, gp130, was upregulated in response to IL-27 in HIV negative individuals, however, in HIV positive individuals, this IL-27 response was diminished. Furthermore, we observed downregulation of IL-27-induced IL-6, TNF-α, and IL-10 expression in HIV positive subjects.ConclusionIn HIV infection, IL-27-induced gene expression was impaired, indicating HIV-mediated dysregulation of IL-27 functions occurs during HIV infection. This study provides evidence for new viral pathogenic mechanisms contributing to the widespread impairment of immune responses observed in HIV pathogenesis.
Highlights
In order for the immune system to clear viral infections, immune cells must be able to produce and respond to cytokines
In HIV infection, IL-27-induced gene expression was impaired, indicating HIV-mediated dysregulation of IL-27 functions occurs during HIV infection
We examined the possibility that IL-27 treatment could enhance either gp130 or WSX-1 expression in Peripheral blood mononuclear cells (PBMC)
Summary
In order for the immune system to clear viral infections, immune cells must be able to produce and respond to cytokines. During HIV infection, cytokine expression and functions become deregulated, contributing to broad immune dysfunction and disease progression. Interleukin-27 (IL-27) can function as a proor anti-inflammatory cytokine depending on cell type and activation status [1]. The WSX-1 receptor chain was identified as a result of sequence homology with the gp130 chain and, as such, is a characteristic type I cytokine receptor [5,6]. IL-27 can bind with low affinity to WSX-1 in the absence of gp130, for effective signal transduction both IL-27R subunits must be expressed [3,7]. A wide variety of cells respond to IL-27, as co-expression of the IL27R subunits has been reported in endothelial cells, mast cells, activated B cells, monocytes, Langerhan’s cells, activated DCs, and T cells [3,7,8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
