title: PD-1 modulates steady-state and infection-induced IL-10 production in vivo.
abstract: 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, Toxoplasma 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⁻/⁻ DCs 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 Th1 immune response after T. gondii infection.
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; University of Cincinnati, College of Medicine, Cincinnati, OH, USA.
authors.forename: Cortez
authors.initials: C
authors.lastname: McBerry
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dias
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Shryock
authors.forename: Kristin
authors.initials: K
authors.lastname: Lampe
authors.forename: Fredy R S
authors.initials: FR
authors.lastname: Gutierrez
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: R Herbert
authors.initials: RH
authors.lastname: De'Broski
authors.forename: Julio
authors.initials: J
authors.lastname: Aliberti
mesh_terms: D000818:Animals; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000378:metabolism*
chemical_list: C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: IL-10; PD-1; Toxoplasma gondii