title: DC-Derived IL-10 Modulates Pro-inflammatory Cytokine Production and Promotes Induction of CD4+IL-10+Regulatory T Cells duringPlasmodium yoeliiInfection.
abstract: The cytokine IL-10 plays a crucial role during malaria infection by counteracting the pro-inflammatory immune response. We and others demonstrated thatPlasmodium yoeliiinfection results in enhanced IL-10 production in CD4+T cells accompanied by the induction of an immunosuppressive phenotype. However, it is unclear whether this is a direct effect caused by the parasite or an indirect consequence due to T cell activation by IL-10-producing antigen-presenting cells. Here, we demonstrate that CD11c+CD11b+CD8-dendritic cells (DCs) produce elevated levels of IL-10 afterP. yoeliiinfection of BALB/c mice. DC-specific ablation of IL-10 inP. yoelii-infected IL-10flox/flox/CD11c-cre mice resulted in increased IFN-γ and TNF-α production with no effect on MHC-II, CD80, or CD86 expression in CD11c+DCs. Accordingly, DC-specific ablation of IL-10 exacerbated systemic IFN-γ and IL-12 production without alteringP. yoeliiblood stage progression. Strikingly, DC-specific inactivation of IL-10 inP. yoelii-infected mice interfered with the induction of IL-10-producing CD4+T cells while raising the frequency of IFN-γ-secreting CD4+T cells. These results suggest thatP. yoeliiinfection promotes IL-10 production in DCs, which in turn dampens secretion of pro-inflammatory cytokines and supports the induction of CD4+IL-10+T cells.
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen , Essen , Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Loevenich
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen , Essen , Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Ueffing
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen , Essen , Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Abel
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen , Essen , Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hose
authors.affiliation: Institute of Biology, Humboldt University, Berlin, Germany; Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Matuschewski
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen , Essen , Germany.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Westendorf
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen , Essen , Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen , Essen , Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hansen
keywords: interleukin 10; malaria; parasitic protozoan; regulatory T cells; rodent