Immunological studies of chronic ocular toxoplasmosis: Up-regulation of major histocompatibility complex class I and transforming growth factor ß and a protective role for interleukin-6

Lyons, R. and Anthony, J. and Ferguson, D.J.P. and Byrne, N. and Alexander, J. and Roberts, F. and Roberts, C.W. (2001) Immunological studies of chronic ocular toxoplasmosis: Up-regulation of major histocompatibility complex class I and transforming growth factor ß and a protective role for interleukin-6. Infection and Immunity, 69 (4). pp. 2589-2595. ISSN 0019-9567

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 beta 2-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 beta , 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-1alpha and increased tumor necrosis factor alpha 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 gondii bradyzoite-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.

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