期刊
PLOS ONE
卷 8, 期 10, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0078146
关键词
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资金
- Canadian Institutes of Health Research [103230]
- CANFAR
- Fonds de la Recherche Quebec-Sante (FRQ-S): Therapie cellulaire and Reseau SIDA/Maladies infectieuses, Quebec, Canada
- CIHR Canadian HIV Trials Network [CTN 247]
- CANFAR/CTN Postdoctoral Fellowship Award
Tryptophan (Trp) catabolism into immunosuppressive kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO) was previously linked to Th17/Treg differentiation and immune activation. Here we examined Trp catabolism and its impact on Th17/Treg balance in uninfected healthy subjects (HS) and a large cohort of HIV-infected patients with different clinical outcomes: ART-naive, Successfully Treated (ST), and elite controllers (EC). In ART-naive patients, increased IDO activity/expression, together with elevated levels of TNF-alpha and sCD40L, were associated with Treg expansion and an altered Th17/Treg balance. These alterations were normalized under ART. In contrast, Trp 2,3-dioxegenase (TDO) expression was dramatically lower in EC when compared to all other groups. Interestingly, EC displayed a distinctive Trp metabolism characterized by low Trp plasma levels similar to ART-na ve patients without accumulating immunosuppressive Kyn levels which was accompanied by a preserved Th17/Treg balance. These results suggest a distinctive Trp catabolism and Th17/Treg balance in HIV progressors and EC. Thus, IDO-induced immune-metabolism may be considered as a new inflammation-related marker for HIV-1 disease progression.
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