Chronic innate immune activation as a cause of HIV-1 immunopathogenesis

• Published in: Clinical immunology (Orlando, Fla.) Vol. 126; no. 3; pp. 235 - 242
• Main Authors: Boasso, Adriano, Shearer, Gene M
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.03.2008; Elsevier
• Subjects: Adaptive immunity; Allergy and Immunology; Biological and medical sciences; Dendritic Cells - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; HIV Infections - immunology; HIV Infections - pathology; HIV Infections - virology; HIV-1 - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunity, Innate - immunology; Immunopathogenesis; Indoleamine 2,3-dioxygenase; Innate immunity; Models, Immunological; Plasmacitoid dendritic cells (pDC); Simian immunodeficiency virus; T cells; Type I interferon; Plasmacitoid dendritic cells (pDC); Type I interferon; Immunopathogenesis; Innate immunity; Indoleamine 2,3-dioxygenase; Adaptive immunity; Human immunodeficiency virus; Simian immunodeficiency virus; T cells; Dendritic cell; HIV-1 virus; Tcells; Enzyme; Cytokine; Retroviridae; Activation; Lentivirus; Immunity; Virus; Chronic; Immunology; Indoleamine-pyrrole 2,3-dioxygenase; Interferon; Oxidoreductases
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2007.08.015

Abstract Human immunodeficiency virus (HIV)-1 infection causes progressive impairment of the immune system in humans, characterized by depletion of CD4 T cells and loss of T cell function. Increased markers of T cell activation and lymphoid hyperplasia suggest that chronic T cell activation persists in immunocompromised hosts, and contributes to the exhaustion of immune functions. Here we propose a revision of this hypothesis, in which we suggest that chronic activation of innate immunity may negatively affect adaptive T cell-mediated responses. We hypothesize that constant exposure of the effector cells of innate immunity to HIV results in their chronic hyperactivation, with deleterious effects on T cells. In particular, plasmacytoid dendritic cells (pDC) may be highly susceptible to HIV-induced activation due to its interaction with the cellular receptor CD4, expressed by pDC. Subsequent production of type I interferon and indoleamine 2,3-dioxygenase may exert suppressive and cytotoxic effects on T cells.