Dataset Information

Evidence for innate immune system activation in HIV type 1-infected elite controllers.

ABSTRACT:

Background

Elite controllers maintain high CD4(+) T-cell counts and suppress plasma human immunodeficiency virus (HIV) viremia in the absence of antiretroviral therapy (ART). It is unclear whether levels of biomarkers associated with coagulation, monocyte activation, and inflammation, which are linked to HIV-associated mortality, differ among elite controllers, ART recipients with suppressed viremia (plasma HIV type 1 RNA load, <50 copies/mL), and HIV-negative controls.

Methods

A total of 68 elite controllers, 68 ART recipients with suppressed viremia, and 35 HIV-negative participants were evaluated. Levels of biomarkers in cryopreserved plasma were measured by enzyme-linked immunosorbent assay and electrochemiluminescence-based assay. Cryopreserved peripheral blood mononuclear cells were used to assess monocyte phenotype and function and interferon-inducible gene expression (IFIG). Nonparametric testing was used to compare median values among groups.

Results

CD4(+) T-cell counts were similar between elite controllers and HIV-negative controls but significantly lower in ART recipients with suppressed viremia. Levels of C-reactive protein and interleukin 6 were higher and IFIG upregulated in both HIV-positive groups, compared with HIV-negative controls. D-dimer and soluble tissue factor levels were significantly elevated in elite controllers, compared with those in ART recipients with suppressed viremia and HIV-negative controls (P < .01). Monocytes from elite controllers (and ART recipients with suppressed viremia) expressed lower CCR2 and higher CX3CR1 levels than monocytes from HIV-negative controls. In addition, elite controllers had a significantly higher proportion of CD14(++)CD16(+) monocytes, compared with HIV-negative controls.

Conclusion

Elite controllers maintain control of plasma HIV viremia and have evidence of an activated innate immune response.

SUBMITTER: Krishnan S

PROVIDER: S-EPMC3935475 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

Evidence for innate immune system activation in HIV type 1-infected elite controllers.

Krishnan Sonya S Wilson Eleanor M P EM Sheikh Virginia V Rupert Adam A Mendoza Daniel D Yang Jun J Lempicki Richard R Migueles Stephen A SA Sereti Irini I

The Journal of infectious diseases 20131101 6

<h4>Background</h4>Elite controllers maintain high CD4(+) T-cell counts and suppress plasma human immunodeficiency virus (HIV) viremia in the absence of antiretroviral therapy (ART). It is unclear whether levels of biomarkers associated with coagulation, monocyte activation, and inflammation, which are linked to HIV-associated mortality, differ among elite controllers, ART recipients with suppressed viremia (plasma HIV type 1 RNA load, <50 copies/mL), and HIV-negative controls.<h4>Methods</h4>A ...[more]

PMID: 24185941

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Project description:ObjectiveElite controllers, defined as persons maintaining undetectable levels of HIV-1 replication in the absence of antiretroviral therapy, represent living evidence that sustained, natural control of HIV-1 is possible, at least in relatively rare instances. Understanding the complex immunologic and virologic characteristics of these specific patients holds promise for inducing drug-free control of HIV-1 in broader populations of HIV-1 infected patients.DesignWe used an unbiased transcriptional profiling approach to characterize CD8+ T cells, the strongest correlate of HIV-1 immune control identified thus far, in a large cohort of elite controllers (n = 51); highly active antiretrovial therapy (HAART)-treated patients (n = 32) and HIV-1 negative (n = 10) served as reference cohorts.MethodsWe isolated mRNA from total CD8+ T cells isolated from peripheral blood mononuclear cell (PBMC) of each individual followed by microarray analysis of the transcriptional signatures.ResultsWe observed profound transcriptional differences [590 transcripts, false discovery rate (FDR)-adjusted P < 0.05] between elite controller and HAART-treated patients. Interestingly, metabolic and signalling pathways governed by mammalian target of rapamycin (mTOR) and eIF2, known for their key roles in regulating cellular growth, proliferation and metabolism, were among the top functions enriched in the differentially expressed genes, suggesting a therapeutically actionable target as a distinguishing feature of spontaneous HIV-1 immune control. A subsequent bootstrapping approach distinguished five different subgroups of elite controller, each characterized by distinct transcriptional signatures. However, despite this marked heterogeneity, differential regulation of mTOR and eIF2 signalling remained the dominant functional pathway in three of these elite controller subgroups.ConclusionThese studies suggest that mTOR and eIF2 signalling may play a remarkably universal role for regulating CD8 T-cell function from elite controllers.

Dataset Information

Evidence for innate immune system activation in HIV type 1-infected elite controllers.

Background

Methods

Results

Conclusion

Publications

Evidence for innate immune system activation in HIV type 1-infected elite controllers.

Similar Datasets

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