title: Distinct tryptophan catabolism and Th17/Treg balance in HIV progressors and elite controllers.
abstract: 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.
authors.affiliation: Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada ; Research Institute, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Mital
authors.initials: M
authors.lastname: Patel
authors.forename: Ido
authors.initials: I
authors.lastname: Kema
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kanagaratham
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
authors.forename: Paméla
authors.initials: P
authors.lastname: Thébault
authors.forename: Réjean
authors.initials: R
authors.lastname: Lapointe
authors.forename: Cécile
authors.initials: C
authors.lastname: Tremblay
authors.forename: Norbert
authors.initials: N
authors.lastname: Gilmore
authors.forename: Petronela
authors.initials: P
authors.lastname: Ancuta
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D014364:Tryptophan