Distinct tryptophan catabolism and Th17/Treg balance in HIV progressors and elite controllers

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 cohor...

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Veröffentlicht in:PloS one 2013-10, Vol.8 (10), p.e78146-e78146
Hauptverfasser: Jenabian, Mohammad-Ali, Patel, Mital, Kema, Ido, Kanagaratham, Cynthia, Radzioch, Danuta, Thébault, Paméla, Lapointe, Réjean, Tremblay, Cécile, Gilmore, Norbert, Ancuta, Petronela, Routy, Jean-Pierre
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Sprache:eng
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Zusammenfassung: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-naïve, Successfully Treated (ST), and elite controllers (EC). In ART-naïve patients, increased IDO activity/expression, together with elevated levels of TNF-α 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-naïve 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0078146