title: Neutrophils in antiretroviral therapy-controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment.
abstract: BACKGROUND
  Despite control of HIV infection under antiretroviral therapy (ART), immune T-cell activation persists in patients with controlled HIV infection, who are at higher risk of inflammatory diseases than the general population. PMNs play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in cases of excessive or misdirected responses.
  
  
  OBJECTIVE
  The aim of our study was to analyze PMN functions in 60 ART-treated and controlled HIV-infected patients (viral load, <20 RNA copies/mL; CD4 count, ≥ 350 cells/mm(3)) with (HIV[I] group) and without (HIV[NI] group) diseases related to an inflammatory process and to compare them with 22 healthy control subjects.
  
  
  METHODS
  Flow cytometry was used to evaluate PMN functions in whole-blood conditions. We studied in parallel the activation markers of T lymphocytes and monocytes and the proinflammatory cytokine environment.
  
  
  RESULTS
  Blood samples from HIV-infected patients revealed basal PMN hyperactivation associated with deregulation of the apoptosis/necrosis equilibrium. Interestingly, this hyperactivation was greater in HIV(I) than HIV(NI) patients and contrasted with a lack of monocyte activation in both groups. The percentage of circulating cells producing IL-17 was also significantly higher in HIV-infected patients than in control subjects and was positively correlated with markers of basal PMN activation. In addition, the detection of IL-22 overproduction in HIV(NI) patients suggests that it might contribute to counteracting chronic inflammatory processes during HIV infection.
  
  
  CONCLUSIONS
  This study thus demonstrates the presence of highly activated PMNs in HIV-infected patients receiving effective ART and the association of these cells with a specific IL-17/IL-22 environment.
authors.affiliation: Sorbonne University, UPMC University Paris 06, Paris, France; INSERM, Centre d'Immunologie et des Maladies Infectieuses, UMR-S CR7, INSERM U1135, Paris, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Campillo-Gimenez
authors.affiliation: Sorbonne University, UPMC University Paris 06, Paris, France; INSERM, Centre d'Immunologie et des Maladies Infectieuses, UMR-S CR7, INSERM U1135, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Casulli
authors.affiliation: AP-HP, Hôpital Pitié-Salpêtrière, Service des maladies infectieuses et tropicales, Paris, France; Sorbonne University, UPMC University Paris 06, UMR-S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris, France.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Dudoit
authors.affiliation: AP-HP, Hôpital Pitié-Salpêtrière, Service des maladies infectieuses et tropicales, Paris, France; Sorbonne University, UPMC University Paris 06, UMR-S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Seang
authors.affiliation: INSERM, Centre d'Immunologie et des Maladies Infectieuses, UMR-S CR7, INSERM U1135, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France.
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
authors.affiliation: Sorbonne University, UPMC University Paris 06, UMR-S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de Virologie, Paris, France.
authors.forename: Sidonie
authors.initials: S
authors.lastname: Lambert-Niclot
authors.affiliation: INSERM, Centre d'Immunologie et des Maladies Infectieuses, UMR-S CR7, INSERM U1135, Paris, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
authors.affiliation: INSERM, Centre d'Immunologie et des Maladies Infectieuses, UMR-S CR7, INSERM U1135, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.affiliation: AP-HP, Hôpital Pitié-Salpêtrière, Service des maladies infectieuses et tropicales, Paris, France; Sorbonne University, UPMC University Paris 06, UMR-S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.affiliation: Sorbonne University, UPMC University Paris 06, Paris, France; INSERM, Centre d'Immunologie et des Maladies Infectieuses, UMR-S CR7, INSERM U1135, Paris, France. Electronic address: carole.elbim@upmc.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Elbim
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D044966:Anti-Retroviral Agents; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22
keywords: HIV; IL-17; IL-18; IL-22; Neutrophils; inflammation