Loading…

Interleukin-6-driven inflammatory response induces retinal pathology in a model of ocular toxoplasmosis reactivation

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 reacti...

Full description

Saved in:
Bibliographic Details
Published in:Infection and immunity 2015-05, Vol.83 (5), p.2109-2117
Main Authors: Rochet, Élise, Brunet, Julie, Sabou, Marcela, Marcellin, Luc, Bourcier, Tristan, Candolfi, Ermanno, Pfaff, Alexander W
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0019-9567
1098-5522
DOI:10.1128/iai.02985-14