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

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

Journal of immunology (Baltimore, Md. : 1950). 2010;185(4):2482-92.

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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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Type of resource:
Content type:
Publication type:
Published date:
Abbreviated journal title:
ISSN:
Place of publication:
United States
Volume:
185
Issue:
4
Pagination:
2482-92
Digital Object Identifier:
10.4049/jimmunol.0904019
Pubmed Identifier:
20631310
Pii Identifier:
jimmunol.0904019
Access state:
Active

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Academic department(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:158622
Created by:
Couper, Kevin
Created:
6th April, 2012, 11:18:22
Last modified by:
Couper, Kevin
Last modified:
14th February, 2016, 20:23:18

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