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

Findlay, E.G., Greig, R, Stumhofer, JS, Hafalla, JC, de, Souza JB, Saris, CJ, Hunter, CA, Riley, EM and Couper, KN (2010) Essential role for IL-27 receptor signaling in prevention of Th1-mediated immunopathology during malaria infection. Journal of immunology (Baltimore, Md. : 1950), 185 (4), 2482–2492. (doi:10.4049/jimmunol.0904019).

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.

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Contributors

Author: E.G. Findlay

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