Efficacy of IL‐17A mAbs on Toxoplasma gondii proliferation and intraocular inflammation in a murine model of ocular toxoplasmosis

Abstract

Abstract Purpose The aims of our study are to determine the possible efficacy of IL‐17A mAbs on Toxoplasma gondii proliferation and the benefit on intraocular inflammation in a murine model of ocular toxoplasmosis. Methods 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, IL‐27 and ROR‐gammaT are quantified using RT‐PCR. Cytokines levels and profiles are established on murine aqueous humor using multiplex assay. Results 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, Foxp3 and IL‐27 are increased with IL‐17 abs. mRNA‐ROR‐gammaT levels are unchanged. In aqueous humor, cytokines pattern shows a Th1/Treg profile after IL‐17 mAbs intraocular injection. Conclusion 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 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.