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A. Sauer, M. Scholler, A. Pfaff, O. Villard, C. Speeg-Schatz, T. Bourcier, E. Candolfi; In a Murine Acute Ocular Toxoplasmosis, Intravitreal Injection of Il-17a Mabs Results in Decreased Toxoplasma Proliferation, Reduced Inflammation and Enhanced Treg Expression. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5238.
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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 Th17 and T regulatory (Treg) cells that play the ‘lead’ role in adaptive immunity to Toxoplasma gondii. The aims of our study are to determine the possible efficacy of IL-17A mAbs on parasite proliferation and the benefit on intraocular inflammation in a murine model of ocular toxoplasmosis.
Mice infection is done by intravitreal injection of Toxoplasma gondii, PRU type II strain, and leads to severe ocular inflammation. At the same time of infection, IL-17A mAbs is administered by intravitreal route. Intraocular inflammatory grading and histological datas are determined. Parasites counting and mRNA levels of Tbet, Foxp3 and ROR-gammaT are quantified using RT-PCR. Cytokines levels and profiles are established on murine aqueous humor using multiplex assay.
Intraocular inflammation is significantly decreased after IL-17A mAbs intravitreal injection in infected mice. Parasite counting shows a significant decrease after IL-17A mAbs. mRNA levels of T-bet and Foxp3 are increased with IL-17 abs. mRNA-ROR-gammaT levels are unchanged. In aqueous humor, cytokines pattern shows a Treg profile after IL-17 mAbs intraocular injection.
IL-17A mAbs may mitigate chorioretinitis by antagonizing the Th17 phenotype through induction of Th1 and Treg cells in the eye. T regulatory (Treg) cells secreting IL-10 and IL-27 could play an important protective and homeostatic role in modulating hypersensitivity responses induced by Toxoplasma infection. Antagonism of Th17 by Treg cells could be a way to limit ocular lesion. These data open new in vivo therapeutic approaches by repressing the Th17 pathway using IL-17A mAbs.
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