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PD ‐1 modulates steady‐state and infection‐induced IL ‐10 production in vivo
Author(s) -
McBerry Cortez,
Dias Alexandra,
Shryock Nathaniel,
Lampe Kristin,
Gutierrez Fredy R. S.,
Boon Louis,
Herbert De'Broski R.,
Aliberti Julio
Publication year - 2014
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201343658
Subject(s) - toxoplasma gondii , biology , immune system , in vivo , inflammation , cytokine , interleukin 10 , immunology , in vitro , parasite hosting , antibody , genetics , world wide web , computer science
Programmed death‐1 ( PD ‐1) plays an important role in mediating immune tolerance through mechanisms that remain unclear. Herein, we investigated whether PD ‐1 prevents excessive host tissue damage during infection with the protozoan parasite, T oxoplasma gondii . Surprisingly, our results demonstrate that PD ‐1‐deficient mice have increased susceptibility to T . gondii , with increased parasite cyst counts along with reduced type‐1 cytokine responses ( IL ‐12 and IFN ‐γ). PD ‐1 −/− DC s showed no cell intrinsic defect in IL ‐12 production in vitro. Instead, PD ‐1 neutralization via genetic or pharmacological approaches resulted in a striking increase in IL ‐10 release, which impaired type‐1‐inflammation during infection. Our results indicate that the absence of PD ‐1 increases IL ‐10 production even in the absence of infection. Although the possibility that such increased IL ‐10 protects against autoimmune damage is speculative, our results show that IL ‐10 suppresses the development of protective T h1 immune response after T . gondii infection.