Research Progress on the Relationship between the NLRP3 Inflammasome and Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy

Abstract

Human immunodeficiency virus (HIV) infection is characterized not only by severe immunodeficiency but also by persistent inflammation and immune activation. These characteristics persist in people living with HIV (PLHIV) receiving effective antiretroviral therapy (ART) and are associated with morbidity and mortality in nonacquired immunodeficiency syndrome (AIDS) events. ART can inhibit HIV replication and promote immune reconstitution, which is currently the most effective way to control AIDS. However, despite effective long-term ART and overall suppression of plasma HIV RNA level, PLHIV still shows chronic low-level inflammation. The exact mechanisms that trigger chronic inflammation are unknown. Activation of the inflammasome is essential for the host response to pathogens, and some recent studies have confirmed the role of the inflammasome in the pathogenesis of inflammatory diseases. The NLRP3 inflammasome has been widely studied, which is a pyrin domain-containing protein 3 belonging to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent studies suggest that inflammasome-mediated pyroptosis is associated with CD4+ T cell loss in the absence of persistent infectious HIV replication. This article reviews the mechanism of the NLRP3 inflammasome and its correlation with immune reconstitution in PLHIV treated with ART.

Race between virus and inflammasomes: inhibition or escape, intervention and therapy

“…As the name suggests, AIDS is characterized by severe immunodeficiency and persistent inflammation ( Shi et al., 2022 ). HIV-1 mainly destroys the immune system by attacking host immune cells (mainly CD4 + T cells), so a marked reduction of circulating CD4 + T cells is a major feature of AIDS ( Galloway et al., 2015 ).…”

Antiretroviral Therapy-Induced Dysregulation of Gene Expression and Lipid Metabolism in HIV+ Patients: Beneficial Role of Antioxidant Phytochemicals

“…Untreated HIV-infected persons present lower levels of HDL-C than HIV-negative people; HDL-C levels are lower after the acquisition of the virus [ 95 , 96 ]. It has been demonstrated in apoE−/− mice that the accumulation of abnormal metabolites such as oxLDL upregulates purinergic 2X7 receptor (P2X7R), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, and interleukin (IL)-1β expression during atherosclerotic plaque formation through protein kinase R (PKR) phosphorylation [ 97 , 98 ]. In HIV infection, HIV-1 transactivator of transcription protein (Tat) and HIV-1 protease increase NLRP3 inflammasome [ 99 ] and contribute to CD4+ T loss through pyroptosis [ 100 ].…”

Factors Associated with Periodontitis in Patients with and without HIV

“…Recent studies point to the potential of periodontitis, even in its early stages, to increase serum and salivary concentrations of NLRP3, an important inflammatory marker that determines the activation of IL-1 β and its proinflammatory properties that include the recruitment of neutrophils and other cells' innate immune systems [ 28 ]. Elevation of this biomarker has also been indicated as a complicating factor involved in the process of controlling chronic diseases [ 29 ] such as diabetes [ 30 ], cardiovascular diseases [ 31 ], and HIV [ 32 , 33 ].…”