Tryptophan catabolism and immune activation in primary and chronic HIV infection

Abstract

BackgroundKynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. We hypothesized that early cART initiation results in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR prior to cART is a predictor of the magnitude of subsequent reduction in immune activation.MethodsProspective study including 57 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/μL, N = 24), late presenters (<200 CD4+ T cells/μL, N = 19)). Kynurenine and tryptophan were analysed by liquid chromatography–tandem mass spectrometry. Total CD4+ and CD8+ T cells were determined and proportion of activated CD38 + HLA-DR+ Tcells was measured using flow cytometry at baseline and after 6 and 12 months of cART.ResultsAt baseline, primary HIV infection had higher KTR than early presenters. However, similar KTR in primary HIV infection and early presenters was found after cART initiation, while late presenters had higher KTR at all time points. In primary HIV infection and early presenters, KTR was positively associated with proportion of activated cells at baseline. Furthermore, in early presenters the KTR at baseline was associated with proportion of activated cells after 6 and 12 months. Interestingly, in primary HIV infection the KTR at baseline was positively associated with reduction in proportion of CD8 + CD38 + HLA-DR T cells after 6 and 12 months.ConclusionsLower kynurenine/tryptophan ratio during follow-up was found after early initiation of cART. KTR in primary HIV infection and early presenters was positively associated with immune activation. Importantly, KTR in primary HIV infection predicted the magnitude of subsequent reduction in immune activation. Thus, a beneficial effect of early cART on KTR was suggested.

Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV-2 Infection

“… 50 Kynurenine/tryptophan is a general measure of indole 2,3-dioxygenase (IDO) which has an immunoregulatory role and is induced by interferon-gamma in response to viral infection. 49 IDO is responsible for the conversion of tryptophan to kynurenine and is a negative regulator of inflammation and this plays a significant role in limiting lung inflammation, but this is clearly perturbed given the elevated levels of Glyc A.…”

Immune signatures for HIV-1 and HIV-2 induced CD4+T cell dysregulation in an Indian cohort

“…Systemic immune activation is a feature of chronic HIV infection and determines the rate of disease progression [17, 18, 40]. HIV-2 infection has been reported to be associated with slower disease progression as compared to HIV-1.However the data available with respect to immune activation associated with infection is limited, conflicting and has reported on either CD4 or CD8 compartment in isolation [41–44].…”

Indoleamine 2, 3-Dioxygenase-Mediated Tryptophan Catabolism: A Leading Star or Supporting Act in the Tuberculosis and HIV Pas-de-Deux?

“…Specific mechanisms of immune impairment are beyond the scope of this review; however, it is noted that aspects of T cell exhaustion persist in the face of chronic immune activation (Brenchley et al, 2006; Doitsh et al, 2014; Doitsh and Greene, 2016; Sokoya et al, 2017). In the last three decades, a wealth of information has indicated that IDO activation and its associated metabolites play a role in human HIV infection and early progression to AIDS (Fuchs et al, 1990; Hunt et al, 2014; Jenabian et al, 2015; Mehraj and Routy, 2015; Gelpi et al, 2017). Tryptophan catabolism and its immune-regulatory effect are notable during HIV progression (Almeida et al, 2009; Mehraj and Routy, 2015; Gelpi et al, 2017; Gautam et al, 2018).…”

“…In the last three decades, a wealth of information has indicated that IDO activation and its associated metabolites play a role in human HIV infection and early progression to AIDS (Fuchs et al, 1990; Hunt et al, 2014; Jenabian et al, 2015; Mehraj and Routy, 2015; Gelpi et al, 2017). Tryptophan catabolism and its immune-regulatory effect are notable during HIV progression (Almeida et al, 2009; Mehraj and Routy, 2015; Gelpi et al, 2017; Gautam et al, 2018). There is a strong association of elevated IDO activity with AIDS-defining illnesses (Nagamatsu and Schust, 2010; Catalfamo et al, 2012; Martinez and Gordon, 2014; Sokoya et al, 2017).…”