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

R. Lyons, J.P. Anthony, D.J.P. Ferguson, N. Byrne, J. Alexander, F. Roberts, C.W. Roberts

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.
LanguageEnglish
Pages2589-2595
Number of pages7
JournalInfection and Immunity
Volume69
Issue number4
DOIs
Publication statusPublished - Apr 2001

Fingerprint

Ocular Toxoplasmosis
Transforming Growth Factor beta1
Major Histocompatibility Complex
Interleukin-6
Up-Regulation
Reverse Transcriptase Polymerase Chain Reaction
Parasites
Infection
Inflammation
beta 2-Microglobulin
Vitreous Body
Messenger RNA
Toxoplasma
Transforming Growth Factor beta
Disease Progression
Retina
Tumor Necrosis Factor-alpha
Immunohistochemistry
Cytokines
Genes

Keywords

  • animals
  • chronic diseases
  • eye
  • female
  • gene expression regulation
  • histocompatibility antigens class I
  • immunohistochemistry
  • interleukin-6
  • mice
  • toxoplasma
  • toxoplasmosis, ocular
  • transforming growth factor beta
  • up-regulation
  • beta 2-microglobulin

Cite this

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title = "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",
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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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. / Lyons, R.; Anthony, J.P.; Ferguson, D.J.P.; Byrne, N.; Alexander, J.; Roberts, F.; Roberts, C.W.

In: Infection and Immunity, Vol. 69, No. 4, 04.2001, p. 2589-2595.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Immunological studies of chronic ocular toxoplasmosis

T2 - Infection and Immunity

AU - Lyons, R.

AU - Anthony, J.P.

AU - Ferguson, D.J.P.

AU - Byrne, N.

AU - Alexander, J.

AU - Roberts, F.

AU - Roberts, C.W.

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AB - 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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KW - eye

KW - female

KW - gene expression regulation

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KW - immunohistochemistry

KW - interleukin-6

KW - mice

KW - toxoplasma

KW - toxoplasmosis, ocular

KW - transforming growth factor beta

KW - up-regulation

KW - beta 2-microglobulin

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DO - 10.1128/IAI.69.4.2589-2595.2001

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JF - Infection and Immunity

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