CD4 + T cells from HIV-1 patients with impaired Th1 effector responses to Mycobacterium tuberculosis exhibit diminished histone and nucleoprotein signatures

Seu, Lillian; Mobley, James A.; Goepfert, Paul

doi:10.1016/j.clim.2017.05.018

Cited by 4 publications

(2 citation statements)

References 54 publications

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“…Additionally, it prevents DNA methylation across the gene bodies of inducible genes in Arabidopsis, thus, augmenting their responsiveness to stimuli. However, in spite of the emerging role of H2A.Z in disease development, including cancer [36–38], HIV [39] and cardiac hypertrophy [22], we have limited knowledge regarding the mechanisms regulating its expression, under physiological or pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A

Shin¹,

He²,

Yang³

et al. 2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The mechanisms that regulate H2A.Z and its requirement for transcription in differentiated mammalian cells remains ambiguous. In this study, we identified the interaction between the C-terminus of ANP32e and N-terminus of H2A.Z in a yeast two-hybrid screen. Knockdown of ANP32e resulted in proteasomal degradation and nuclear depletion of H2A.Z or of a chimeric green florescence protein fused to its N-terminus. This effect was reversed by inhibition of protein phosphatase 2A (PP2A) and, conversely, reproduced by overexpression of its catalytic subunit. Accordingly, knockdown of ANP32e inhibited phosphorylation of H2A.Z, whereas a mutation of serine-9 proved its requirement for both the protein's stability and nuclear localization, as did knockdown of the nuclear mitogen and stress-induced kinase 1. Moreover, ANP32e's knockdown also revealed its differential requirement for cell signaling and gene expression, whereas, genome-wide binding analysis confirmed its co-localization with H2A.Z at transcription start sites, as well as, gene bodies of inducible and tissue-specific genes. The data also suggest that H2A.Z restricts transcription, which is moderated by ANP32e at the promoter and gene bodies of expressed genes. Thus, ANP32e, through inhibition of PP2A, is required for nucleosomal inclusion of H2A.Z and the regulation of gene expression.

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Section: Discussionmentioning

confidence: 99%

Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A

Shin¹,

He²,

Yang³

et al. 2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…Regulatory CD4 + T cells (Tregs) secrete transforming growth factor beta (TGF-β) and IL-10, which regulate self-tolerance and the immune response in infectious diseases, preventing an excessive immune response by suppressive action [ 8 ]. This functional alteration of the immune system (deregulation) has been related to gut mucosal barrier dysfunction, dysbiosis, and residual inflammation [ 9 ]; persistent immune activation [ 4 ]; HIV persistence [ 10 ]; and increased risk for tuberculosis [ 11 , 12 ] and pneumococcal colonization [ 13 ] in HIV-infected patients on cART.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status

García-Broncano

Medrano

Berenguer

et al. 2018

Cells

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Background: Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4+ T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liver stiffness measure (LSM)] and their linear relationship. Methods: We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had <12.5 kPa, 73 had 12.5–25 kPa, and 46 had >25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results: We found HIV/HCV-coinfected patients had higher values of CD4+ Tregs (p < 0.001), memory Tregs (p ≤ 0.001), and plasma cytokine levels [IFN-γ (p ≤ 0.05) and IL-10 (p ≤ 0.01)] compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83; p = 0.019), IL-2 (aAMR = 0.78; p = 0.017), TNF-α (aAMR = 0.67; p < 0.001), and IL-17A (aAMR = 0.75; p = 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66; p = 0.021), TNF-α (aAMR = 0.565; p = 0.003), and IL-17A (aAMR = 0.58; p = 0.003) than patients with <12.5 kPa. Conclusion: HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response.

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T Cell Responses during Human Immunodeficiency Virus/Mycobacterium tuberculosis Coinfection

Bohórquez,

Jagannath,

et al. 2024

Vaccines

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Coinfection with Mycobacterium tuberculosis (Mtb) and the human immunodeficiency virus (HIV) is a significant public health concern. Individuals infected with Mtb who acquire HIV are approximately 16 times more likely to develop active tuberculosis. T cells play an important role as both targets for HIV infection and mediators of the immune response against both pathogens. This review aims to synthesize the current literature and provide insights into the effects of HIV/Mtb coinfection on T cell populations and their contributions to immunity. Evidence from multiple in vitro and in vivo studies demonstrates that T helper responses are severely compromised during coinfection, leading to impaired cytotoxic responses. Moreover, HIV’s targeting of Mtb-specific cells, including those within granulomas, offers an explanation for the severe progression of the disease. Herein, we discuss the patterns of differentiation, exhaustion, and transcriptomic changes in T cells during coinfection, as well as the metabolic adaptations that are necessary for T cell maintenance and functionality. This review highlights the interconnectedness of the immune response and the pathogenesis of HIV/Mtb coinfection.

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CD4 + T cells from HIV-1 patients with impaired Th1 effector responses to Mycobacterium tuberculosis exhibit diminished histone and nucleoprotein signatures

Cited by 4 publications

References 54 publications

Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A

Transcriptional regulation mediated by H2A.Z via ANP32e-dependent inhibition of protein phosphatase 2A

Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status

T Cell Responses during Human Immunodeficiency Virus/Mycobacterium tuberculosis Coinfection

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