Essential role for IL-27 receptor signaling in prevention of Th1-mediated immunopathology during malaria infection

Emily Gwyer Findlay, Rachel Greig, Jason S Stumhofer, Julius C R Hafalla, J Brian de Souza, Christiaan J Saris, Christopher A Hunter, Eleanor M Riley, Kevin N Couper

Research output: Contribution to journalArticlepeer-review

Abstract

Successful resolution of malaria infection requires induction of proinflammatory immune responses that facilitate parasite clearance; however, failure to regulate this inflammation leads to immune-mediated pathology. The pathways that maintain this immunological balance during malaria infection remain poorly defined. In this study, we demonstrate that IL-27R-deficient (WSX-1(-/-)) mice are highly susceptible to Plasmodium berghei NK65 infection, developing exacerbated Th1-mediated immune responses, which, despite highly efficient parasite clearance, lead directly to severe liver pathology. Depletion of CD4(+) T cells---but not CD8(+) T cells---prevented liver pathology in infected WSX-1(-/-) mice. Although WSX-1 signaling was required for optimal IL-10 production by CD4(+) T cells, administration of rIL-10 failed to ameliorate liver damage in WSX-1(-/-) mice, indicating that additional, IL-10-independent, protective pathways are modulated by IL-27R signaling during malaria infection. These data are the first to demonstrate the essential role of IL-27R signaling in regulating effector T cell function during malaria infection and reveal a novel pathway that might be amenable to manipulation by drugs or vaccines.

Original languageEnglish
Pages (from-to)2482-92
Number of pages11
JournalJournal of Immunology
Volume185
Issue number4
DOIs
Publication statusPublished - 15 Aug 2010

Keywords

  • Animals
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cytokines
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Interferon-gamma
  • Interleukin-10
  • Interleukin-17
  • Liver
  • Lymphocyte Count
  • Malaria
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Parasitemia
  • Plasmodium berghei
  • Receptors, Cytokine
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Th1 Cells

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