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: Élise Rochet, Julie Brunet, Marcela Sabou, Luc Marcellin, Tristan Bourcier, Ermanno Candolfi, Alexander W Pfaff
• Journal: Infection and immunity (Infect Immun) Vol. 83 Issue 5 Pg. 2109-17 (May 2015) ISSN: 1098-5522 [Electronic] United States
• PMID: 25754200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Interleukin-17
• Interleukin-6
• interleukin-6, mouse
• Interferon-gamma

Topics

• Animals
• Disease Models, Animal
• Female
• Interferon-gamma (metabolism)
• Interleukin-17 (metabolism)
• Interleukin-6 (immunology)
• Mice
• Mice, Inbred C57BL
• Parasite Load
• Retina (pathology)
• Time Factors
• Toxoplasma (immunology)
• Toxoplasmosis, Ocular (immunology, parasitology, pathology)