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C. Subauste, J.-A. Portillo, J. Wadell; CD40 Mediates Resistance Against Ocular Toxoplasmosis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1115.
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Ocular toxoplasmosis is the most common cause of infectious retinitis worldwide. IFN-Î³ is an important mediator of resistance against this disease. However, there is increasing evidence that the immune system can control certain pathogens independently of IFN-Î³. We previously reported that CD40 activates macrophages to kill Toxoplasma gondii in the absence of IFN-Î³. We conducted experiments to determine if CD40 mediates resistance against ocular toxoplasmosis and whether such an effect is independent of IFN-Î³.
C57BL/6 and CD40-/- mice were infected with tissue cysts of T. gondii. Eyes were collected for histopathology, DNA isolation to assess parasite load by real time PCR and determination of cytokine mRNA levels using real time RT-PCR. Serum IFN-Î³ was measured by ELISA.Microglia was isolated from mixed glial retinal culture.
While C57BL/6 mice chronically infected with T. gondii develop minimal inflammation in the retina, CD40-/- mice exhibited marked distortion of the retinal architecture, more intense inflammatory infiltrates and areas of retinal necrosis. This was accompanied by an increase in parasite load in the eye. Ocular toxoplasmosis in CD40-/- mice developed despite unimpaired mRNA levels of IFN-Î³ and NOS2 in the eye and elevated serum levels of IFN-Î³. Retinal microglia from mice express CD40. Moreover, CD40 stimulation of microglia resulted in killing of T. gondii independently of IFN-Î³.
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