title: Interleukin-6-driven inflammatory response induces retinal pathology in a model of ocular toxoplasmosis reactivation.
abstract: Ocular inflammation is one of the consequences of infection with the protozoan parasite Toxoplasma gondii. Even if lesions are self-healing in immunocompetent persons, they pose a lifetime risk of reactivation and are a serious threat to vision. As there are virtually no immunological data on reactivating ocular toxoplasmosis, we established a model of direct intravitreal injection of parasites in previously infected mice with a homologous type II strain. Two different mouse strains with variable ability to control retinal infection were studied in order to describe protective and deleterious reaction patterns. In Swiss-Webster mice, which are already relatively resistant to primary infection, no peak of parasite load was observed upon reinfection. In contrast, the susceptible inbred strain C57BL/6 showed high parasite loads after 7 days, as well as marked deterioration of retinal architecture. Both parameters were back to normal on day 21. C57BL/6 mice also reacted with a strong local production of inflammatory and Th1-type cytokines, like interleukin-6 (IL-6), IL-17A, and gamma interferon (IFN-γ), while Swiss-Webster mice showed only moderate expression of the Th2 cytokine IL-31. Interestingly, rapid intraocular production of anti-Toxoplasma antibodies was observed in Swiss-Webster but not in C57BL/6 mice. We then localized the cellular source of different immune mediators within the retina by immunofluorescence. Finally, neutralization experiments of IFN-γ or IL-6 demonstrated the respective protective and deleterious roles of these cytokines for parasite control and retinal integrity during reinfection. In conclusion, we developed and immunologically characterized a promising mouse model of reactivating ocular toxoplasmosis.
authors.affiliation: Institut de Parasitologie et Pathologie Tropicale, Fédération de Médecine Translationnelle, Université de Strasbourg, Strasbourg, France.
authors.forename: Élise
authors.initials: É
authors.lastname: Rochet
authors.affiliation: Institut de Parasitologie et Pathologie Tropicale, Fédération de Médecine Translationnelle, Université de Strasbourg, Strasbourg, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Brunet
authors.affiliation: Institut de Parasitologie et Pathologie Tropicale, Fédération de Médecine Translationnelle, Université de Strasbourg, Strasbourg, France.
authors.forename: Marcela
authors.initials: M
authors.lastname: Sabou
authors.affiliation: Service de Pathologie, Centre Hospitalier Universitaire, Strasbourg, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Marcellin
authors.affiliation: Service d'Ophtalmologie, Centre Hospitalier Universitaire, Strasbourg, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Bourcier
authors.affiliation: Institut de Parasitologie et Pathologie Tropicale, Fédération de Médecine Translationnelle, Université de Strasbourg, Strasbourg, France.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Candolfi
authors.affiliation: Institut de Parasitologie et Pathologie Tropicale, Fédération de Médecine Translationnelle, Université de Strasbourg, Strasbourg, France pfaff@unistra.fr.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Pfaff
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D012160:Retina / Q000473:pathology*; D013997:Time Factors; D014122:Toxoplasma / Q000276:immunology*; D014126:Toxoplasmosis, Ocular / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; C577686:interleukin-6, mouse; D007371:Interferon-gamma