IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii

Leigh A Jones, Fiona Roberts, Mohammad B Nickdel, Frank Brombacher, Andrew N J McKenzie, Fiona L Henriquez, James Alexander, Craig W. Roberts

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

T1/ST2 is an immunoregulatory protein of the IL-1 receptor family that has recently been reported as being a component of the IL-33 receptor. IL-33 is a newly described cytokine known to amplify the Th2 response and reduce production of Th1 cytokines. The function of T1/ST2 during Toxoplasma gondii infection is as yet undescribed. Given the requirement of a balanced type 1/type 2 response for effective control of parasite number and immunopathology, it is likely that T1/ST2 may play a part in aiding this process. Accordingly, we have shown that T1/ST2 mRNA transcripts are upregulated in the brains of mice infected with T. gondii and that mice deficient in T1/ST2 demonstrated increased susceptibility to infection with T. gondii that correlated with increased pathology and greater parasite burden in the brains. Real-time PCR analysis of cerebral cytokine levels revealed increased mRNA levels of iNOS, IFN-gamma and TNF-alpha in infected T1/ST2(-/-) mice. These effects were independent of changes in IL-10 production. This study provides the first evidence of a specific role for IL-33 receptor signalling in the brain as well as highlighting the requirement of this mechanism in limiting infection with an intracellular parasite.

Original languageEnglish
Pages (from-to)426-36
Number of pages11
JournalJournal of Clinical Immunology
Volume40
Issue number2
DOIs
Publication statusPublished - Feb 2010
Externally publishedYes

Fingerprint

Toxoplasma
Encephalitis
Toxoplasmosis
Cytokines
Brain
Parasites
Communicable Disease Control
Messenger RNA
Interleukin-1 Receptors
Interleukin-10
Real-Time Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Pathology
Infection
Interleukin-33
Proteins

Keywords

  • Animals
  • Body Weight
  • Brain
  • Encephalitis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Interferon-gamma
  • Interleukin-4
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nitric Oxide Synthase Type II
  • Receptors, Cell Surface
  • Receptors, Interleukin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Toxoplasma
  • Toxoplasmosis, Animal
  • Transcriptional Activation
  • Tumor Necrosis Factor-alpha

Cite this

Jones, Leigh A ; Roberts, Fiona ; Nickdel, Mohammad B ; Brombacher, Frank ; McKenzie, Andrew N J ; Henriquez, Fiona L ; Alexander, James ; Roberts, Craig W. / IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii. In: Journal of Clinical Immunology. 2010 ; Vol. 40, No. 2. pp. 426-36.
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IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii. / Jones, Leigh A; Roberts, Fiona; Nickdel, Mohammad B; Brombacher, Frank; McKenzie, Andrew N J; Henriquez, Fiona L; Alexander, James; Roberts, Craig W.

In: Journal of Clinical Immunology, Vol. 40, No. 2, 02.2010, p. 426-36.

Research output: Contribution to journalArticle

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T1 - IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii

AU - Jones, Leigh A

AU - Roberts, Fiona

AU - Nickdel, Mohammad B

AU - Brombacher, Frank

AU - McKenzie, Andrew N J

AU - Henriquez, Fiona L

AU - Alexander, James

AU - Roberts, Craig W.

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AB - T1/ST2 is an immunoregulatory protein of the IL-1 receptor family that has recently been reported as being a component of the IL-33 receptor. IL-33 is a newly described cytokine known to amplify the Th2 response and reduce production of Th1 cytokines. The function of T1/ST2 during Toxoplasma gondii infection is as yet undescribed. Given the requirement of a balanced type 1/type 2 response for effective control of parasite number and immunopathology, it is likely that T1/ST2 may play a part in aiding this process. Accordingly, we have shown that T1/ST2 mRNA transcripts are upregulated in the brains of mice infected with T. gondii and that mice deficient in T1/ST2 demonstrated increased susceptibility to infection with T. gondii that correlated with increased pathology and greater parasite burden in the brains. Real-time PCR analysis of cerebral cytokine levels revealed increased mRNA levels of iNOS, IFN-gamma and TNF-alpha in infected T1/ST2(-/-) mice. These effects were independent of changes in IL-10 production. This study provides the first evidence of a specific role for IL-33 receptor signalling in the brain as well as highlighting the requirement of this mechanism in limiting infection with an intracellular parasite.

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JO - Journal of Clinical Immunology

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