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Ira Blader, Tiffany Kley, Kevin Brown, Felix Yarovinsky; MyD88 is Essential to Detect Toxoplasma gondii in the Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2780.
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Toxoplasma gondii is the causative agent of ocular toxoplasmosis, which is one of the most common infectious diseases of the posterior retina. The prevalence of this infection is directly due to the parasite’s ability to establish a chronic retinal infection and reside within a quiescent cyst. Occasionally these cysts reactivate within the retina and a potentially blinding disease will develop unless the host can mount a properly regulated immune response. The initial phase of this response is typified by recruitment of monocytes and neutrophils to the retina and the IFNγ-dependent upregulation of MHC Class II and PD-L1 on both infiltrating leukocytes and resident retinal cells. The triggering of this immune response is dependent on retinal recognition of the parasites but how Toxoplasma is detected in the retina is unknown. Here, we tested the hypothesis that the innate sensor protein MyD88 and Toll-like receptors (TLRs) are required to detect Toxoplasma in the retina.
C57BL/6 WT, MyD88-/-, and various TLR knockout mice were intravitreally injected with Toxoplasma tachyzoites. After 6 days post infection, the eyes were harvested and retinal inflammatory responses were compared between the two mice. Specifically we used ELISAs to measure IFNγ protein levels and FACS to assess MHC Class II and PD-L1 expression levels as well as monocyte and neutrophil infiltration.
In contrast to wild-type mice, blood-derived monocytes and neutrophils were not recruited to retinas of Toxoplasma-infected MyD88 knockout mice. Similarly, resident retinal cell of MHC Class II and PD-L1 expression was negligible in intravitreally infected MyD88 knockout mice. Experiments are currently underway to define which TLR receptor(s) signal(s) upstream of myd88 in parasite-infected eyes.
Our data demonstrate that MyD88 is absolutely essential for Toxoplasma to be recognized in the retina. This is different than in other tissues where MyD88 is an important but not the only innate parasite sensing molecule.
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