Balance of Th17 and T Regulatory Responses in Murine Models of Ocular Toxoplasmosis

Abstract

Purpose: : Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. Taking into account the opposing needs of limiting parasite multiplication and minimizing tissue destruction, the infection imbalance implies especially CD4 and CD8 T lymphocytes that play the ‘lead’ role in adaptive immunity to Toxoplasma gondii. The aims of our study are to determine the cytokine pattern in human aqueous humor and to develop murine models of toxoplasmosic uveitis (TU).

Methods: : Seventeen aqueous humor from patients presenting a confirmed TU were investigated for their cytokine pattern using bio-assay multiplex. Data were compared to those obtained from patients complaining of cataract or non infectious uveitis. Two murine models were also studied : (i) Primary infection by intravitreal injection of Toxoplasma, (ii) Reinfection by parasite intraperitoneal inoculation at birth and challenge by intravitreal injection. Clinical and histological data were determined and compared to mRNA-cytokine ocular levels.

Results: : In human uveitis, interleukin (IL)-5 and IL-12 were detected and were specific for TU. IFN-gamma, TNF-alpha, IL-17, IL-6, IL-10 and IL-4 were detected in both UT and non infectious uveitis. In murine models, primary infection led to severe chorioretinitis, when compared with reinfection. mRNA levels of IL-27, Foxp3 and IL-10 were increased in the reinfection model. At the opposite, mRNA levels of TGF-b, IL-17 and ROR-gT were increased in the primary infection model.

Keywords: toxoplasmosis • immunomodulation/immunoregulation • uveitis-clinical/animal model