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. © 2014, American Society for Microbiology.
    Original languageEnglish
    Pages (from-to)10-20
    Number of pages10
    JournalInfection and immunity
    Volume82
    Issue number1
    DOIs
    Publication statusPublished - Jan 2014

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