Mechanisms of systemic low-grade inflammation in HIV patients on long-term suppressive antiretroviral therapy: the inflammasome hypothesis.

Autor:	Guerville F; University Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, INSERM ERL 1303., Vialemaringe M; University Bordeaux, INSERM, Institut Bergonié, BPH, U1219, CIC-EC 1401., Cognet C; CHU Bordeaux, Laboratory of Immunology and Immunogenetics., Duffau P; University Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, INSERM ERL 1303.; CHU Bordeaux, Service de Médecine Interne et Immunologie Clinique., Lazaro E; University Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, INSERM ERL 1303.; CHU Bordeaux, Service de Médecine Interne., Cazanave C; CHU Bordeaux, Infectious and Tropical Diseases department., Bonnet F; University Bordeaux, INSERM, Institut Bergonié, BPH, U1219, CIC-EC 1401.; CHU Bordeaux, Hôpital Saint-André, Service de Médecine Interne et Maladies Infectieuses., Leleux O; University Bordeaux, INSERM, Institut Bergonié, BPH, U1219, CIC-EC 1401., Rossignol R; INSERM U1211, 33000 Bordeaux, France; Bordeaux University; CELLOMET, Functional Genomics Center (CGFB), 146 rue Léo Saignat., Pinson B; Service Analyses Métaboliques TBMcore CNRS UAR 3427 INSERM US005 Université de Bordeaux, 1 rue Camille Saint-Saëns., Tumiotto C; CHU Bordeaux, Laboratory of Virology., Gabriel F; CHU Bordeaux, Laboratory of Parasitology, Bordeaux., Appay V; University Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, INSERM ERL 1303., Déchanet-Merville J; University Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, INSERM ERL 1303., Wittkop L; University Bordeaux, INSERM, Institut Bergonié, BPH, U1219, CIC-EC 1401.; INRIA SISTM team, Talence.; CHU de Bordeaux, Service d'information médicale, INSERM, Institut Bergonié, CIC-EC 1401, Bordeaux, France., Faustin B; University Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, INSERM ERL 1303.; Immunology Discovery, Janssen Research & Development, San Diego, California, USA., Pellegrin I; University Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, INSERM ERL 1303.; CHU Bordeaux, Laboratory of Immunology and Immunogenetics.
Jazyk:	angličtina
Zdroj:	AIDS (London, England) [AIDS] 2023 Jun 01; Vol. 37 (7), pp. 1035-1046. Date of Electronic Publication: 2023 Mar 14.
DOI:	10.1097/QAD.0000000000003546
Abstrakt:	Objective: We aimed to determine the contribution of inflammasome activation in chronic low-grade systemic inflammation observed in patients with HIV (PWH) on long-term suppressive antiretroviral therapy (ART) and to explore mechanisms of such activation. Design: Forty-two PWH on long-term suppressive ART (HIV-RNA < 40 copies/ml) were compared with 10 HIV-negative healthy controls (HC). Methods: Inflammasome activation was measured by dosing mature interleukin (IL)-1β and IL-18 cytokines in patient serum. We explored inflammasome pathways through ex vivo stimulation of PWH primary monocytes with inflammasome activators; expression of inflammasome components by transcriptomic analysis; and metabolomics analysis of patient sera. Results: Median (Q1; Q3) age, ART and viral suppression duration in PWH were 54 (48; 60), 15 (9; 20) and 7.5 (5; 12) years, respectively. Higher serum IL-18 was measured in PWH than in HC (61 (42; 77) vs. 36 (27-48 pg/ml), P = 0.009); IL-1β was detected in 10/42 PWH (0.5 (0.34; 0.80) pg/ml) but not in HC. Monocytes from PWH did not produce more inflammatory cytokines in vitro , but secretion of IL-1β in response to NOD like receptor family, pyrin domain containing 3 (NLRP3) inflammasome stimulation was higher than in HC. This was not explained at the transcriptional level. We found an oxidative stress molecular profile in PWH sera. Conclusion: HIV infection with long-term effective ART is associated with a serum inflammatory signature, including markers of inflammasome activation, and an increased activation of monocytes upon inflammasome stimulation. Other cells should be investigated as sources of inflammatory cytokines in PWH. Oxidative stress might contribute to this chronic low-grade inflammation. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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