title: Interleukin 17A as an effective target for anti-inflammatory and antiparasitic treatment of toxoplasmic uveitis.
abstract: BACKGROUND
  Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. The requirement of limiting both parasite multiplication and tissue destruction suggests that the balance between T-helper (Th) 17 and T-regulatory cells is an important factor in toxoplasmosis-induced retinal damage.
  
  
  METHODS
  In a prospective clinical study of acute ocular toxoplasmosis, we assessed the cytokine pattern in aqueous humors of 10 affected patients. To determine the immunological mechanisms, we evaluated intraocular inflammation, parasite load, and immunological responses using messenger RNA and protein levels in a mouse model. Anti-interleukin 17A (IL-17A) monoclonal antibodies (mAbs) were administered with the parasite to evaluate the role of IL-17A.
  
  
  RESULTS
  Severe ocular inflammation and cytokine patterns comparable to human cases were observed, including IL-17A production. Neutralizing IL-17A decreased intraocular inflammation and parasite load in mice. Detailed studies revealed up-regulation of T-regulatory and Th1 pathways. When interferon γ (IFN-γ) was neutralized concomitantly, the parasite multiplication rate was partially restored.
  
  
  CONCLUSIONS
  Local IL-17A production by resident cells plays a central role in the pathology of ocular toxoplasmosis. The balance between Th17 and Th1 responses (especially IFN-γ) is crucial for the outcome of infection. This data reveals new in vivo therapeutic approaches by repressing inflammatory pathways using intravitreal injection of IL-17A mAbs.
authors.affiliation: Service d'Ophtalmologie, Centre Hospitalier Universitaire de Strasbourg, Cedex, France. arnaud.sauer@chru-strasbourg.fr
authors.forename: Arnaud
authors.initials: A
authors.lastname: Sauer
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Pfaff
authors.forename: Odile
authors.initials: O
authors.lastname: Villard
authors.forename: Catherine
authors.initials: C
authors.lastname: Creuzot-Garcher
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dalle
authors.forename: Christophe
authors.initials: C
authors.lastname: Chiquet
authors.forename: Hervé
authors.initials: H
authors.lastname: Pelloux
authors.forename: Claude
authors.initials: C
authors.lastname: Speeg-Schatz
authors.forename: David
authors.initials: D
authors.lastname: Gaucher
authors.forename: Gilles
authors.initials: G
authors.lastname: Prevost
authors.forename: Tristan
authors.initials: T
authors.lastname: Bourcier
authors.forename: Ermanno
authors.initials: E
authors.lastname: Candolfi
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000276:immunology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D059208:Parasite Load; D011446:Prospective Studies; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D014126:Toxoplasmosis, Ocular / Q000150:complications* / Q000276:immunology* / Q000469:parasitology; D015866:Uveitis, Posterior / Q000276:immunology* / Q000469:parasitology
chemical_list: C508717:IL17A protein, human; C098680:Il17a protein, mouse; D020381:Interleukin-17; D007371:Interferon-gamma