Indoleamine 2,3 Dioxygenase, Age, and Immune Activation in People Living with Hiv

Abstract

Immune activation complicates HIV despite antiretroviral therapy (ART). Indoleamine 2,3 dioxygenase (IDO) catabolizes tryptophan (T) to kynurenine (K), regulating immune activity, and IDO activity increases with age. This study examines the relationship of IDO activity, bacterial translocation, and aging in people living with HIV (PLWH) on ART. Samples and data from PLWH on ART from the Centers for AIDS Research Network of Integrated Clinical Systems and from matched HIV-uninfected patients (controls) from the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study were analyzed. The ratio of K to T (K:T) and neopterin were indicators of inflammation; 16S ribosomal DNA (16S rDNA) and lipopolysaccharide (LPS) were markers of bacterial translocation. Samples and data from 205 PLWH and 99 controls were analyzed. PLWH had higher K:T values across all ages, with a significant relationship between age and K:T for both groups. CD4 count or CD4 nadir had no association with K:T. There was no positive association between level of 16S rDNA or LPS detection and K:T. K:T and neopterin were associated. PLWH had elevated IDO activity, at younger ages, despite ART. This study suggests K:T ratio increases with age in both groups and is elevated in PLWH at all ages compared with age-matched controls.

T-cell activation and B-cell interaction signatures in rectal tissues are associated with HIV replication in ex-vivo model of infection

“…Indeed, neither of the two downregulated DEG, CHRNA1 (log 2 fold ¼ À1.14, P adj ¼ 0.003) and SER-PINA6 (log 2 fold ¼ À0.89, P adj ¼ 0.007), has been associated with restricting HIV replication. Conversely, the upregulated DEG identified in this study with the greatest significance, IDO1, codes for an enzyme in the kynurenine pathway important in the suppression of inflammation and the development of immune tolerance (log 2 fold ¼ 2.09, P adj ¼ 2.55E À 07) [23] and has been positively associated with HIV pathogenesis after HIV infection [24,25]. Additional genes involved in tryptophan catabolism were also positively associated with p24 production but did not meet our conservative threshold for DEG significance (TDO2, KMO, KYNU, P adj < 0.05) [26].…”

Depressive-like Behavior Is Accompanied by Prefrontal Cortical Innate Immune Fatigue and Dendritic Spine Losses after HIV-1 Tat and Morphine Exposure

“…Increases in IL-1β, TNFα, and IL-6 are accompanied by elevations in IDO levels in the whole brains of mice 4 h after a single icv Tat injection, followed by increased depressive-like behavior 24 h after Tat exposure [ 61 ]. Increased levels of IDO are found in PWH and associated with increased neuropsychiatric symptoms [ 150 ] and inflammation despite viral suppression with ART [ 151 ]. In a similar Tat tg model with multiple tat gene copy numbers and more aggressive pathology, increased striatal serotonin and 5-HIAA levels are associated with increased reward response thresholds in an intracranial self-stimulation paradigm after 3 days of Tat exposure [ 93 ].…”

Survival and prognostic factors of progressive multifocal leukoencephalopathy in people living with HIV in modern ART era

“…differentiation toward regulatory T cells and away from helper cells (Th-17) (Huang et al, 2020: Baer et al, 2021. Previous researches showed that increased plasma IDO activity is associated with HIV disease progression and mortality in PLWH (Pertovaara et al, 2006;Chen et al, 2014;Jenabian et al, 2015).…”