Plasma Indoleamine 2,3-Dioxygenase Activity Is Associated With the Size of the Human Immunodeficiency Virus Reservoir in Patients Receiving Antiretroviral Therapy

Chen, Jun; Xun, Jingna; Yang, Junyang; Ji, Yongjia; Liu, Li; Qi, Tangkai; Wang, Zhenyan; Zhang, Renfang; Shen, Yinzhong; Ponte, Rosalie; Mehraj, Vikram; Routy, Jean‐Pierre; Lu, Hongzhou

doi:10.1093/cid/ciy676

Cited by 48 publications

(45 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The plasma K/T ratio was significantly higher in South African MDR-TB patients both with and without HIV coinfection versus controls ( Figure 3A). Persons with TB disease coinfected with HIV had a higher plasma K/T ratio versus persons with TB disease alone (P = 0.01), consistent with prior observations that HIV also induces tryptophan catabolism (28,29). The plasma K/T ratio again demonstrated excellent classification accuracy for active TB disease (AUC = 0.92; Figure 3C), and a cutoff of 0.03 had a sensitivity of 99% in both cohorts.…”

Section: Resultssupporting

confidence: 84%

“…If tryptophan catabolism modulates T cell responses to create tolerance, such immune modulation may be protective in the central nervous system, where robust inflammatory responses are generally detrimental (47). In conditions such as HIV and pregnancy, which similarly induce IDO-mediated tryptophan catabolism (29,44), further study is needed to determine whether this may contribute to the elevated TB progression risk observed in these populations (48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tryptophan catabolism reflects disease activity in human tuberculosis

Collins¹,

Siddiqa²,

Jones³

et al. 2020

JCI Insight

View full text Add to dashboard Cite

Section: Resultssupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Tryptophan catabolism reflects disease activity in human tuberculosis

Collins¹,

Siddiqa²,

Jones³

et al. 2020

JCI Insight

View full text Add to dashboard Cite

“…We also showed that IDO-1 activity and Treg frequency were strongly correlated with plasma βDG. We, as well as others, have shown that increased IDO-1 activity is linked to an increased frequency of Tregs, epithelial gut damage, degree of microbial translocation, immune activation, HIV disease progression, and HIV reservoir size [15,25,28,[31][32][33]. Because IDO-1 is known to be expressed in myeloid cells, which also express βDG receptors, these findings suggest that elevated βDG may participate in the induction of IDO-1 activity.…”

Section: Discussionsupporting

confidence: 60%

Circulating (1→3)-β-D-glucan Is Associated With Immune Activation During Human Immunodeficiency Virus Infection

Study

Mehraj

Ramendra

et al. 2019

Clinical Infectious Diseases

Self Cite

124

View full text Add to dashboard Cite

Background Microbial translocation from the gut to systemic circulation contributes to immune activation during human immunodeficiency virus (HIV) infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Fungal colonization in the gut increases during HIV-infection and people living with HIV (PLWH) have increased plasma levels of fungal polysaccharide (1→3)-β-D-Glucan (βDG). We assessed the contribution of circulating DG to systemic immune activation in PLWH. Methods Cross-sectional and longitudinal assessments of plasma βDG levels were conducted along with markers of HIV disease progression, epithelial gut damage, bacterial translocation, proinflammatory cytokines, and βDG-specific receptor expression on monocytes and natural killer (NK) cells. Results Plasma βDG levels were elevated during early and chronic HIV infection and persisted despite long-term antiretroviral therapy (ART). βDG increased over 24 months without ART but remained unchanged after 24 months of treatment. βDG correlated negatively with CD4 T-cell count and positively with time to ART initiation, viral load, intestinal fatty acid–binding protein, LPS, and soluble LPS receptor soluble CD14 (sCD14). Elevated βDG correlated positively with indoleamine-2,3-dioxygenase-1 enzyme activity, regulatory T-cell frequency, activated CD38+Human Leukocyte Antigen - DR isotype (HLA-DR)+ CD4 and CD8 T cells and negatively with Dectin-1 and NKp30 expression on monocytes and NK cells, respectively. Conclusions PLWH have elevated plasma βDG in correlation with markers of disease progression, gut damage, bacterial translocation, and inflammation. Early ART initiation prevents further βDG increase. This fungal antigen contributes to immune activation and represents a potential therapeutic target to prevent non–acquired immunodeficiency syndrome events.

show abstract

“…Although it was not mechanistically interrogated, a positive association between plasma indoleamine 2,3-dioxygenase (IDO) activity (an immunoregulatory enzyme that metabolizes tryptophan) and total HIV DNA in peripheral blood has been established. 68 Impaired intestinal barrier integrity is a classical feature of HIV infection, characterized by dysbiosis and increased microbial by-products that drive systemic and mucosal in ammation. 69,70 Microbes with the capacity to catabolize tryptophan have been linked to adverse HIV disease progression, 71 at least in part due to induction of IDO1 that interferes with Th17/Treg balance in the periphery and gut.…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

Giron

Palmer

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the pathways involved in post-ART HIV control. We identified plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-rebound using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. The signatures remained significant after adjusting for key demographic and clinical confounders. We also confirmed a mechanistic link between biomarkers and HIV latency reactivation and myeloid inflammation in vitro. Finally, machine learning algorithms selected sets of biomarkers that predict time-to-viral-rebound with 74–76% capacity and probability-of-viral-rebound with 97.5% capacity. In summary, we fill a major gap in HIV cure research by identifying non-invasive biomarkers, with potential functional significance, that predict duration and probability of viral remission after treatment interruption.

show abstract

Plasma Indoleamine 2,3-Dioxygenase Activity Is Associated With the Size of the Human Immunodeficiency Virus Reservoir in Patients Receiving Antiretroviral Therapy

Abstract: We observed a positive correlation between IDO activity and total HIV DNA in blood, highlighting the important role of immunometabolic aberrations in HIV persistence.

Cited by 48 publications

References 40 publications

Tryptophan catabolism reflects disease activity in human tuberculosis

Tryptophan catabolism reflects disease activity in human tuberculosis

Circulating (1→3)-β-D-glucan Is Associated With Immune Activation During Human Immunodeficiency Virus Infection

Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

Contact Info

Product

Resources

About