title: Immunosuppressive Tryptophan Catabolism and Gut Mucosal Dysfunction Following Early HIV Infection.
abstract: BACKGROUND
  Tryptophan (Trp) catabolism into kynurenine (Kyn) contributes to immune dysfunction in chronic human immunodeficiency virus (HIV) infection. To better define the relationship between Trp catabolism, inflammation, gut mucosal dysfunction, and the role of early antiretroviral therapy (ART), we prospectively assessed patients early after they acquired HIV.
  
  
  METHODS
  Forty patients in the early phase of infection were longitudinally followed for 12 months after receiving a diagnosis of HIV infection; 24 were untreated, and 16 were receiving ART. Kyn/Trp ratio, regulatory T-cells (Tregs) frequency, T-cell activation, dendritic cell counts, and plasma levels of gut mucosal dysfunction markers intestinal-type fatty acid-binding protein, soluble suppression of tumorigenicity 2, and lipopolysaccharide were assessed.
  
  
  RESULTS
  Compared with healthy subjects, patients in the early phase of infection presented with elevated Kyn/Trp ratios, which further increased in untreated patients but normalized in ART recipients. Accordingly, in untreated subjects, the elevated Treg frequency observed at baseline continued to increase over time. The highest CD8(+) T-cell activation was observed during the early phase of infection and decreased in untreated patients, whereas activation normalized in ART recipients. The Kyn/Trp ratio was positively associated with CD8(+) T-cell activation and levels of inflammatory cytokines (interleukin 6, interferon γ-inducible protein 10, interleukin 18, and tumor necrosis factor α) and negatively associated with dendritic cell frequencies at baseline and in untreated patients. However, ART did not normalize plasma levels of gut mucosal dysfunction markers.
  
  
  CONCLUSIONS
  Early initiation of ART normalized enhanced Trp catabolism and immune activation but did not improve plasma levels of gut mucosal dysfunction markers.
authors.affiliation: Chronic Viral Illnesses Service Research Institute.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.affiliation: CHUM Research Centre.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Far
authors.affiliation: Chronic Viral Illnesses Service Research Institute.
authors.forename: Kishanda
authors.initials: K
authors.lastname: Vyboh
authors.affiliation: Department of Laboratory Medicine, University Medical Center, University of Groningen, The Netherlands.
authors.forename: Ido
authors.initials: I
authors.lastname: Kema
authors.affiliation: Chronic Viral Illnesses Service Division of Infectious Diseases.
authors.forename: Cecilia T
authors.initials: CT
authors.lastname: Costiniuk
authors.affiliation: Clinique Médicale l'Actuel.
authors.forename: Rejean
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Clinique Médicale Quartier Latin.
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Baril
authors.affiliation: Chronic Viral Illnesses Service Clinique Médicale OPUS.
authors.forename: Roger
authors.initials: R
authors.lastname: LeBlanc
authors.affiliation: Research Institute.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kanagaratham
authors.affiliation: Research Institute.
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
authors.affiliation: Department of Microbiology and Immunology CHU Ste-Justine Research Center, University of Montreal, Quebec, Canada.
authors.forename: Ossama
authors.initials: O
authors.lastname: Allam
authors.affiliation: Department of Microbiology and Immunology CHU Ste-Justine Research Center, University of Montreal, Quebec, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Chronic Viral Illnesses Service.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lebouché
authors.affiliation: CHUM Research Centre Department of Microbiology and Immunology.
authors.forename: Cécile
authors.initials: C
authors.lastname: Tremblay
authors.affiliation: CHUM Research Centre Department of Microbiology and Immunology.
authors.forename: Petronela
authors.initials: P
authors.lastname: Ancuta
authors.affiliation: Chronic Viral Illnesses Service Research Institute Division of Hematology, McGill University Health Centre.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007737:Kynurenine / Q000276:immunology / Q000378:metabolism; D008137:Longitudinal Studies; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014364:Tryptophan / Q000276:immunology* / Q000378:metabolism
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D007737:Kynurenine; D014364:Tryptophan
keywords: ART; HIV early infection; dendritic cells; gut mucosal dysfunction; indoleamine 2,3-dioxygenase-1 (IDO-1); inflammation; microbial translocation; regulatory T-cells (Tregs); sST2; tryptophan