IL-27 Receptor Signaling Regulates Memory CD4+ T Cell Populations and Suppresses Rapid Inflammatory Responses during Secondary Malaria Infection

Emily Gwyer Findlay, Ana Villegas-Mendez, Noelle O'Regan, J Brian de Souza, Lisa-Marie Grady, Christiaan J Saris, Eleanor M Riley, Kevin N Couper

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin-27 (IL-27) is known to control primary CD4+ T cell responses during a variety of different infections, but its role in regulating memory CD4+ T responses has not been investigated in any model. In this study, we have examined the functional importance of IL-27 receptor (IL-27R) signaling in regulating the formation and maintenance of memory CD4+ T cells following malaria infection and in controlling their subsequent reactivation during secondary parasite challenge. We demonstrate that although the primary effector/memory CD4+ T cell response was greater in IL-27R-deficient (WSX-1−/−) mice following Plasmodium berghei NK65 infection than in wild-type (WT) mice, there were no significant differences in the size of the maintained memory CD4+ T population(s) at 20 weeks postinfection in the spleen, liver, or bone marrow of WSX-1−/− mice compared with WT mice. However, the composition of the memory CD4+ T cell pool was slightly altered in WSX-1−/− mice following clearance of primary malaria infection, with elevated numbers of late effector memory CD4+ T cells in the spleen and liver and increased production of IL-2 in the spleen. Crucially, WSX-1−/− mice displayed significantly enhanced parasite control compared with WT mice following rechallenge with homologous malaria parasites. Improved parasite control in WSX-1−/− mice during secondary infection was associated with elevated systemic production of multiple inflammatory innate and adaptive cytokines and extremely rapid proliferation of antigen-experienced T cells in the liver. These data are the first to demonstrate that IL-27R signaling plays a role in regulating the magnitude and quality of secondary immune responses during rechallenge infections.
Original languageEnglish
Pages (from-to)10-20
Number of pages11
JournalInfection and Immunity
Volume82
Issue number1
Early online date7 Oct 2013
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Animals
  • CD4-Positive T-Lymphocytes
  • Cell Count
  • Cytokines
  • Disease Models, Animal
  • Immunity, Cellular
  • Inflammation
  • Interleukins
  • Liver
  • Malaria
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Parasitemia
  • Plasmodium berghei
  • Receptors, Interleukin
  • Signal Transduction
  • Spleen

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