Mechanisms of residual immune activation in HIV-1-infected human lymphoid tissue ex vivo. (1st July 2021)

• Record Type: Journal Article
• Authors: Mercurio, Vincenzo; Fitzgerald, Wendy; Vanpouille, Christophe; Molodtsov, Ivan; Margolis, Leonid
• Is Part Of: AIDS. Volume 35:Number 8(2021)
• Publication Date: 2021-07-01
• Subjects: antiretroviral therapy -- cytokine storm -- ex-vivo tissues -- extracellular vesicles -- HIV -- human herpesvirus -- immune activation; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000002881
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objective: HIV-1 infection triggers immune activation, as reflected by the upregulation of various cytokines. This immune activation remains elevated despite antiretroviral therapy (ART) and leads to early age-related diseases. Here, we addressed the mechanisms of sustained immune activation in HIV-1-infected human lymphoid tissues ex vivo . Design/method: We investigated several potential causes of immunoactivation, including: a proinflammatory effect of ART drugs themselves; an early HIV-1-triggered cytokine storm, which could in turn trigger a sustained cytokine dysregulation; herpesvirus reactivation; HIV-1 protein release; and production of defective virions and extracellular vesicles. Tissue immune activation was evaluated from measurements of cytokines in culture medium using multiplexed immunoassays. Results: Neither ART itself nor simulated cytokine storms nor exogenously added HIV-1 proteins triggered a sustained cytokine upregulation. In contrast, defective (replicative-incompetent) virions and extracellular vesicles induced sustained cytokine upregulation, as did infectious virus. Tissue immune activation was accompanied by reactivation of cytomegalovirus. Conclusion: The system of ex-vivo human lymphoid tissue allowed investigation, under laboratory-controlled conditions, of possible mechanisms involved in persistent immune activation in HIV-1 patients under ART. Mechanisms of this immunoactivation identified in ex-vivo tissues may indicate potential therapeutic targets for restoration of immune system homeostasis in HIV-1-infected patients. Abstract : Supplemental Digital Content is available in the text