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      Activated dendritic cells and monocytes in HIV immunological nonresponders: HIV-induced interferon-inducible protein-10 correlates with low future CD4 + recovery

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          To explore monocyte and dendritic cell immune responses, and their association with future CD4 + gain in treated HIV patients with suboptimal CD4 + recovery.


          A cross-sectional study of HIV-infected, virally suppressed individuals on antiretroviral therapy for at least 24 months; 41 immunological nonresponders (INRs) (CD4 + cell count <400 cells/μl) and 26 immunological responders (CD4 + cell count >600 cells/μl). Ten HIV-infected antiretroviral therapy-naive and 10 HIV-negative healthy persons served as controls. CD4 + cell counts were registered after median 2.4 and 4.7 years.


          Monocyte, dendritic-cell and T-cell activation and regulatory T cells (Tregs) were analyzed by flow cytometry. In INR and immunological responder subgroups matched on age and nadir CD4 + cell count, upregulation of interferon-inducible protein-10 (IP-10) and indoleamine 2,3-dioxygenase in monocytes and dendritic cells and cytokines in cell supernatants were measured in vitro in peripheral blood mononuclear cells stimulated with aldrithiol-2-inactivated HIV-1.


          The INR group displayed higher spontaneous activation of both monocytes (HLA-DR +) and myeloid and plasmacytoid dendritic cells (HLA-DR +, CD83 + and CD86 +) compared with immunological responders, and this was associated with increased T-cell activation (CD38 +HLA-DR +), an effector memory T-cell phenotype and activated Tregs. The IP-10 response in monocytes after in-vitro HIV stimulation was negatively associated with prospective CD4 + gain. IP-10, indoleamine 2,3-dioxygenase and cytokines levels were comparable between the groups, but inversely correlated with activated Tregs in INRs.


          HIV-infected individuals with suboptimal immune recovery demonstrated more activated monocytes and in particular dendritic cells, compared with patients with acceptable CD4 + gain. A high level of HIV-specific IP-10 expression in monocytes may be predictive of future CD4 + recovery.

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          Most cited references 58

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          Microbial translocation is a cause of systemic immune activation in chronic HIV infection.

          Chronic activation of the immune system is a hallmark of progressive HIV infection and better predicts disease outcome than plasma viral load, yet its etiology remains obscure. Here we show that circulating microbial products, probably derived from the gastrointestinal tract, are a cause of HIV-related systemic immune activation. Circulating lipopolysaccharide, which we used as an indicator of microbial translocation, was significantly increased in chronically HIV-infected individuals and in simian immunodeficiency virus (SIV)-infected rhesus macaques (P
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            • Article: not found

            Microbial translocation in HIV infection: causes, consequences and treatment opportunities.

            Systemic immune activation is increased in HIV-infected individuals, even in the setting of virus suppression with antiretroviral therapy. Although numerous factors may contribute, microbial products have recently emerged as potential drivers of this immune activation. In this Review, we describe the intestinal damage that occurs in HIV infection, the evidence for translocation of microbial products into the systemic circulation and the pathways by which these products activate the immune system. We also discuss novel therapies that disrupt the translocation of microbial products and the downstream effects of microbial translocation.
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              Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection.

              While inflammation predicts mortality in treated human immunodeficiency virus (HIV) infection, the prognostic significance of gut barrier dysfunction and phenotypic T-cell markers remains unclear.

                Author and article information

                AIDS (London, England)
                Lippincott Williams & Wilkins
                1 June 2019
                14 February 2019
                : 33
                : 7
                : 1117-1129
                [a ]Department of Infectious Diseases, Oslo University Hospital
                [b ]Institute of Clinical Medicine, Faculty of Medicine, University of Oslo
                [c ]The Flow Cytometry Core Facility, Blood Cell Research Group, Department of Medical Biochemistry, Oslo University Hospital
                [d ]Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital
                [e ]Department of Cancer Immunology, Oslo University Hospital
                [f ]Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo
                [g ]KG Jebsen Thrombosis Research and Expertise Center, Tromsø
                [h ]Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo
                [i ]Department of Clinical Science, University of Bergen, Bergen, Norway.
                Author notes
                Correspondence to Birgitte Stiksrud, Department of Infectious Diseases, Oslo University Hospital, Ullevål, PO Box 4950 Nydalen, N-0424 Oslo, Norway. Tel: +47 99601909; e-mail: birgitte.stiksrud@
                AIDS-D-18-00933 00002
                Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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