<scp>CCR</scp>
            5 deficiency/
            <scp>CCR</scp>
            5Δ32: resistant to
            <scp>HIV</scp>
            infection at the cost of curtailed
            <scp>CD</scp>
            4
            <sup>+</sup>
            T cell memory responses

Matti, Christoph; Legler, Daniel F.

doi:10.15252/embj.2020105854

Cited by 4 publications

(1 citation statement)

References 11 publications

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“…T cells are also exposed to signals provided by chemokines - cytokines that act through seven-transmembrane G-protein-coupled receptors and traditionally catalogued as regulators of leukocyte trafficking ( 28 ). Solid evidence exists, however, that some chemokine receptors influence T-cell fate and function in a chemotactic-independent manner ( 29 ). In particular, C-C chemokine receptor 5 (CCR5) has been implicated in maximizing CD4 + T cell co-stimulation and the induction of transcriptional programs responsible for cytokine production ( 30 – 34 ).…”

Section: Introductionmentioning

confidence: 99%

The Chemokine Receptor CCR5 Links Memory CD4+ T Cell Metabolism to T Cell Antigen Receptor Nanoclustering

et al. 2021

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The inhibition of anabolic pathways, such as aerobic glycolysis, is a metabolic cornerstone of memory T cell differentiation and function. However, the signals that hamper these anabolic pathways are not completely known. Recent evidence pinpoints the chemokine receptor CCR5 as an important player in CD4+ T cell memory responses by regulating T cell antigen receptor (TCR) nanoclustering in an antigen-independent manner. This paper reports that CCR5 specifically restrains aerobic glycolysis in memory-like CD4+ T cells, but not in effector CD4+ T cells. CCR5-deficient memory CD4+ T cells thus show an abnormally high glycolytic/oxidative metabolism ratio. No CCR5-dependent change in glucose uptake nor in the expression of the main glucose transporters was detected in any of the examined cell types, although CCR5-deficient memory cells did show increased expression of the hexokinase 2 and pyruvate kinase M2 isoforms, plus the concomitant downregulation of Bcl-6, a transcriptional repressor of these key glycolytic enzymes. Further, the TCR nanoclustering defects observed in CCR5-deficient antigen-experienced CD4+ T cells were partially reversed by incubation with 2-deoxyglucose (2-DG), suggesting a link between inhibition of the glycolytic pathway and TCR nanoscopic organization. Indeed, the treatment of CCR5-deficient lymphoblasts with 2-DG enhanced IL-2 production after antigen re-stimulation. These results identify CCR5 as an important regulator of the metabolic fitness of memory CD4+ T cells, and reveal an unexpected link between T cell metabolism and TCR organization with potential influence on the response of memory T cells upon antigen re-encounter.

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Section: Introductionmentioning

confidence: 99%

The Chemokine Receptor CCR5 Links Memory CD4+ T Cell Metabolism to T Cell Antigen Receptor Nanoclustering

et al. 2021

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CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

Kulmann-Leal

Ellwanger

2021

Front. Immunol.

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The genetic background of Brazilians encompasses Amerindian, African, and European components as a result of the colonization of an already Amerindian inhabited region by Europeans, associated to a massive influx of Africans. Other migratory flows introduced into the Brazilian population genetic components from Asia and the Middle East. Currently, Brazil has a highly admixed population and, therefore, the study of genetic factors in the context of health or disease in Brazil is a challenging and remarkably interesting subject. This phenomenon is exemplified by the genetic variant CCR5Δ32, a 32 base-pair deletion in the CCR5 gene. CCR5Δ32 originated in Europe, but the time of origin as well as the selective pressures that allowed the maintenance of this variant and the establishment of its current frequencies in the different human populations is still a field of debates. Due to its origin, the CCR5Δ32 allele frequency is high in European-derived populations (~10%) and low in Asian and African native human populations. In Brazil, the CCR5Δ32 allele frequency is intermediate (4-6%) and varies on the Brazilian States, depending on the migratory history of each region. CCR5 is a protein that regulates the activity of several immune cells, also acting as the main HIV-1 co-receptor. The CCR5 expression is influenced by CCR5Δ32 genotypes. No CCR5 expression is observed in CCR5Δ32 homozygous individuals. Thus, the CCR5Δ32 has particular effects on different diseases. At the population level, the effect that CCR5Δ32 has on European populations may be different than that observed in highly admixed populations. Besides less evident due to its low frequency in admixed groups, the effect of the CCR5Δ32 variant may be affected by other genetic traits. Understanding the effects of CCR5Δ32 on Brazilians is essential to predict the potential use of pharmacological CCR5 modulators in Brazil. Therefore, this study reviews the impacts of the CCR5Δ32 on the Brazilian population, considering infectious diseases, inflammatory conditions, and cancer. Finally, this article provides a general discussion concerning the impacts of a European-derived variant, the CCR5Δ32, on a highly admixed population.

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The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection

Shi

Chen

et al. 2022

Front. Immunol.

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The natural process of human immunodeficiency virus type 1(HIV-1) infection is characterized by high viral load, immune cell exhaustion, and immunodeficiency, which eventually leads to the stage of acquired immunodeficiency syndrome (AIDS) and opportunistic infections. Rapidly progressing HIV-1 individuals often die of AIDS several years after infection without treatment. The promotion of ART greatly prolongs the survival time of HIV-infected persons. However, some patients have incomplete immune function reconstruction after ART due to latent storage of HIV-infected cells. Therefore, how to achieve a functional cure has always been the focus and hot spot of global AIDS research. Fortunately, the emergence of ECs/LTNPs who can control virus replication naturally has ignited new hope for realizing a functional cure for AIDS. Recently, a special category of infected individuals has attracted attention that can delay the progression of the disease more rigorously than the natural progression of HIV-1 infection described above. These patients are characterized by years of HIV-1 infection, long-term asymptomatic status, and normal CD4+T cell count without ART, classified as HIV-infected long-term nonprogressors (LTNPs) and elite controllers (ECs). Numerous studies have shown that the host and virus jointly determine the progression of HIV-1 infection, in which the level of innate immunity activation plays an important role. As the first line of defense against pathogen invasion, innate immunity is also a bridge to induce adaptive immunity. Compared with natural progressors, innate immunity plays an antiviral role in HIV-1 infection by inducing or activating many innate immune-related factors in the natural ECs. Learning the regulation of ECs immunity, especially the innate immunity in different characteristics, and thus studying the mechanism of the control of disease progression naturally, will contribute to the realization of the functional cure of AIDS. Therefore, this review will explore the relationship between innate immunity and disease progression in ECs of HIV-1 infection from the aspects of innate immune cells, signaling pathways, cytokines, which is helpful to provide new targets and theoretical references for the functional cure, prevention and control of AIDS, and development of a vaccine.

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CCR 5 deficiency/ CCR 5Δ32: resistant to HIV infection at the cost of curtailed CD 4 ⁺ T cell memory responses

Cited by 4 publications

References 11 publications

The Chemokine Receptor CCR5 Links Memory CD4+ T Cell Metabolism to T Cell Antigen Receptor Nanoclustering

The Chemokine Receptor CCR5 Links Memory CD4+ T Cell Metabolism to T Cell Antigen Receptor Nanoclustering

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection

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CCR 5 deficiency/ CCR 5Δ32: resistant to HIV infection at the cost of curtailed CD 4 + T cell memory responses

Cited by 4 publications

References 11 publications

The Chemokine Receptor CCR5 Links Memory CD4+ T Cell Metabolism to T Cell Antigen Receptor Nanoclustering

The Chemokine Receptor CCR5 Links Memory CD4+ T Cell Metabolism to T Cell Antigen Receptor Nanoclustering

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection

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CCR 5 deficiency/ CCR 5Δ32: resistant to HIV infection at the cost of curtailed CD 4 ⁺ T cell memory responses