Immunological Studies of Chronic Ocular Toxoplasmosis: Up-Regulation of Major Histocompatibility Complex Class I and Transforming Growth Factor β and a Protective Role for Interleukin-6

ABSTRACT A murine model was used to characterize the local immune and inflammatory response during ocular toxoplasmosis. Major histocompatibility complex (MHC) class I, normally expressed at low levels in immune-privileged sites such as the eye, was up-regulated during infection as determined by competitive reverse transcriptase (RT)-PCR and immunocytochemistry for both β2-microglobulin and the MHC class I heavy chain. However, the eyes of chronically infected mice also had increased levels of mRNA transcripts for transforming growth factor β, a cytokine associated with immune privilege and constitutively expressed in normal eyes. Transcripts for a number of inflammatory mediators, including interleukin-6 (IL-6), were increased during chronic infection. The role of IL-6 was further investigated by comparing disease progression and the development of the local immune response in wild-type (WT) and IL-6-deficient mice (IL-6−/− mice). Following infection, IL-6−/− mice developed more severe inflammation in the retina and vitreous humor compared with WT mice. This increased severity of disease was associated with reduced ocular IL-1α and increased tumor necrosis factor α mRNA production compared with WT mice. Moreover, the increased severity of disease in IL-6−/− mice correlated with increased eye parasite burden as determined by RT-PCR for the Toxoplasma gondiibradyzoite-specific LDH2 gene. These results demonstrate alterations to components of immune privilege as a result of ocular toxoplasmosis and a role for IL-6 in controlling parasite numbers and inflammation in the eye.