Nlrp3 and Il-1Β Gene Expression Is Elevated in Monocytes From Hiv-Treated Patients With Neurocognitive Disorders Publisher Pubmed



Mazaheritehrani E¹ ; Mohraz M¹ ; Nasi M² ; Chester J² ; Gaetano AD³ ; Tartaro DL⁴ ; Seyedalinaghi S¹ ; Gholami M¹ ; Biasi SD⁴ ; Gibellini L⁴ ; Mattioli AV^{2, 5} ; Pinti M³ ; Mussini C⁶ ; Cossarizza A^{4, 5} Show Affiliations
Source: Journal of Acquired Immune Deficiency Syndromes Published:2021

Abstract

Background: Systemic immune activation and inflammation in chronic HIV infection are driving factors of non-AIDS-related events, including neurocognitive impairment. The role of inflammasome in monocytes from patients with HIV infection has been extensively studied, but its association with the extent of neurocognitive dysfunction has been poorly investigated. Methods: We enrolled 79 HIV-positive patients; 44 with varying levels of HIV-associated neurocognitive disorder (HAND) and 35 without and 8 healthy donors. HAND subtypes included asymptomatic neurocognitive impairment (asymptomatic neurocognitive impairment; n = 19), mild neurocognitive disorder (MND; n = 17), and HIV-associated dementia (n = 8). We quantified plasmatic concentrations of proinflammatory cytokines (TNF-α, IL-6, IL-17A, IL-1β, and IFN-γ) for all HIV patients, and the mRNA expression of genes involved in the inflammasome activity (NLRP3, PYCARD, NAIP, AIM2, IL-1b, and IL-18) in monocytes of a subgroup of 28 HIV patients and 8 healthy donors. Results: HIV patients' plasma concentrations of IFN-γ, IL-1β, and IL-17A were undetectable. Levels of TNF-α and IL-6 were similar among the HIV patient groups. A trend toward an increased expression of inflammasome genes according to neurocognitive disorder severity was observed. Of note, the NLRP3 mRNA relative expression was higher in MND compared with other groups, and IL- 1b was lower in MND than HIV-associated dementia patients. Conclusions: Changes in inflammasome components in circulating monocytes according to different HAND severity suggest that NLRP3 may be a possible biomarker or target to better understand and treat the link between systemic inflammation and neurocognitive impairment in HIV infection. © 2021 Lippincott Williams and Wilkins. All rights reserved.