Combined antiretroviral therapy (cART) extends the lifespan and the quality of life for HIV-infected persons but does not completely eliminate chronic immune activation and inflammation. The low level of chronic immune activation persisting during cART-treated HIV infection is associated with the development of diseases which usually occur in the elderly. Although T-cell activation has been extensively examined in the context of cART-treated HIV infection, monocyte activation is only beginning to be recognized as an important source of inflammation in this context. Here we examine markers and sources of monocyte activation during cART-treated HIV infection and discuss the role of monocytes during cardiovascular disease, HIV-associated neurocognitive disorder, and innate immune aging.
Background-Mapping T cell epitopes for a pathogen or vaccine requires a complex method for screening hundreds to thousands of peptides with a limited amount of donor sample. We describe an optimized deconvolution process by which peptides are pooled in a matrix format to minimize the number of tests required to identify peptide epitopes.
We report the robustness of silica hydride stationary phase, aqueous normal phase (ANP) chromatography to the chemical complexity of the intracellular metabolomes of Staphylococcus aureus and Enterococcus faecium. We specifically demonstrate that the chromatographic behavior of known metabolites is unaffected by the intracellular chemical matrix of these microbes and that this method enable untargeted profiling of their intracellular metabolites using accurate mass-retention time (AMRT) identifiers. We further demonstrate the ability of AMRT-based metabolite profiling to differentiate bacteria along genetic and phenotypic lines. Overall, these data commend the utility of ANP-based chromatography for untargeted metabolomics-based studies of microbial physiology and antibiotic resistance.
Objective
People living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes up-regulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD.
Methods
Participants with >75th percentile (n=15) and <25th percentile (n=15) age-adjusted intima-media thickness (IMT) at the right common carotid artery and bifurcation were identified from the Women's Interagency HIV Study. Groups were matched by age, race/ethnicity, smoking status, and CD4 count. All women were receiving suppressive antiretroviral therapy except for one high and one low IMT participant. Monocyte and T lymphocyte populations were evaluated for GLUT1 and CD38 expression using flow cytometry.
Results
Intermediate monocytes from high IMT women had significantly increased expression of GLUT1 (310 MFI vs. 210 MFI, p=0.024) (66.4% vs. 48.5%, p=0.031) and CD38 (339 MFI vs. 211 MFI, p=0.002) (10.5% vs. 3.8%, p=0.0002) compared to women with low IMT. High and low IMT participants showed no differences in GLUT1 or CD38 expression on classical monocytes, non-classical monocytes, CD4+ and CD8+ T lymphocytes.
Conclusion
GLUT1-expressing intermediate monocytes are elevated in HIV-infected women with subclinical CVD. These cells may contribute to development of CVD in PLWH and could be a novel target to limit inflammation.
ELISA, and Trillium IgG/IgM rapid assays was evaluated in Jamaica. Methods: Diagnostic sensitivities of the assays were assessed by testing serum samples from SARS-CoV-2 PCR-confirmed persons and diagnostic specificity was assessed by testing serum samples collected during 2018-2019 from healthy persons and from persons with antibodies to a wide range of viral infections.Results: Serum samples collected !14 days after onset of symptoms, or an initial SARS-CoV-2 RT-PCR positive test for asymptomatics, showed diagnostic sensitivities ranging from 67.9 to 75.0% when including all possible disease severities and increased to 90.0-95.0% when examining those with moderate to critical disease. Grouping moderate to critical disease showed a significant association with a SARS-CoV-2 antibody positive result for all assays. Diagnostic specificity ranged from 96.7 to 100.0%. For all assays examined, SARS-CoV-2 real-time PCR cycle threshold (Ct) values of the initial nasopharyngeal swab sample testing positive were significantly different for samples testing antibody positive versus negative. Conclusions: These data from a predominantly African descent Caribbean population show comparable diagnostic sensitivities and specificities for all testing platforms assessed and limited utility of these tests for persons with asymptomatic and mild infections.
Objective:Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4+ T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4+ T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4+ T-cell glucose metabolism in HIV+ women with and without diabetes mellitus.Design:A case–control study was used to compare CD4+ T-cell glucose metabolism in women with HIV with or without diabetes mellitus.Methods:Nondiabetic (HIV+DM−, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4+ cell count. CD4+ T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4+ T cells.Results:HIV+DM+ displayed a significantly elevated proportion of CD4+ T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM− (P = 0.04 and P = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4+ T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM−. T-cell receptor (TCR)-activated CD4+ T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM−.Conclusion:CD4+ T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4+ T-cell metabolic dysfunction.
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