Immunological studies of chronic ocular toxoplasmosis: up-regulation of major histocompatibility complex class I and transforming growth factor beta and a protective role for interleukin-6.
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 beta2-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.
Lyons
R E
RE
Department of Immunology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, Glasgow, Scotland.
Anthony
J P
JP
Ferguson
D J
DJ
Byrne
N
N
Alexander
J
J
Roberts
F
F
Roberts
C W
CW
D000818:Animals; D002908:Chronic Disease; D005123:Eye / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000096:biosynthesis*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D014122:Toxoplasma / Q000302:isolation & purification; D014126:Toxoplasmosis, Ocular / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D001613:beta 2-Microglobulin / Q000032:analysis
D015395:Histocompatibility Antigens Class I; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D001613:beta 2-Microglobulin