Transforming growth factor-β expression in human retinal pigment epithelial cells is enhanced by Toxoplasma gondii: A possible role in the immunopathogenesis of retinochoroiditis

Retinochoroiditis caused by Toxoplasma gondii infection results in inflammation and necrosis of the retina. We have used human retinal pigment epithelial cultures (HRPE) as an in vitro model to investigate the role of TGF-β in T. gondii-induced retinochoroiditis. RT-PCR analyses showed enhanced steady state levels of TGF-β1 and TGF-β2 mRNA in T. gondii-infected HRPE. Uninfected HRPE secrete TGF-β1 in a latent form while 10-30% of the secreted TGF-β2 was in the active form. T. gondii infection induced a significant increase (P <0.01) in total TGF-β1 and TGF-β2 secretion by HRPE. In addition, soluble extracts of T. gondii (ST) stimulated secretion of both TGF-β1 and TGF-β2 significantly (P <0.01). Interestingly, T. gondii infection as well as ST of the parasites completely inhibited secretion of the active form of TGF-β2. Studies evaluating the effect of TGF-β on T. gondii replication in HRPE revealed that TGF-β enhanced parasite replication. The interactions between host retinal cells and T. gondii may play an active role in the pathogenesis of retinochoroiditis.