IL-27 receptor signaling regulates memory CD4+ T cell populations and suppresses rapid inflammatory responses during secondary malaria infection.

Gwyer Findlay, Emily, Villegas-Mendez, Ana, O'Regan, Noelle, de Souza, J. Brian, Grady, Lisa-Marie, Saris, Christiaan J., Riley, Eleanor M. and Couper, Kevin N. (2014) IL-27 receptor signaling regulates memory CD4+ T cell populations and suppresses rapid inflammatory responses during secondary malaria infection. Infection and Immunity, 82 (1), 10 - 20. (doi:10.1128/IAI.01091-13).

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.

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Contributors

Author: Emily Gwyer Findlay

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