AUTHOR=Ueffing Kristina , Abberger Hanna , Westendorf Astrid M. , Matuschewski Kai , Buer Jan , Hansen Wiebke TITLE=Conventional CD11chigh Dendritic Cells Are Important for T Cell Priming during the Initial Phase of Plasmodium yoelii Infection, but Are Dispensable at Later Time Points JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01333 DOI=10.3389/fimmu.2017.01333 ISSN=1664-3224 ABSTRACT=

Dendritic cells (DCs) are highly specialized antigen-presenting cells that orchestrate adaptive immune responses to pathogens. During malaria infection pro- and anti-inflammatory T cell responses have to be tightly balanced to ensure parasite clearance without induction of severe immune pathologies. However, the precise role of CD11c^high DCs in this process is still discussed controversially. Here, we demonstrate that long-term depletion of conventional CD11c^high DCs in Plasmodium yoelii (P. yoelii)-infected diphtheria toxin (DT)-treated RosaiDTR/CD11c-cre mice interferes with the activation of CD8⁺ and CD4⁺ T cells as well as CD4⁺Foxp3⁺ regulatory T cells at early time points during infection. Moreover, systemic levels of the pro-inflammatory cytokines IFN-γ and TNF-α were decreased in P. yoelii-infected mice deficient for CD11c^high DCs compared to infected RosaiDTR controls. To further elucidate the importance of CD11c^high DCs during the later phase of infection, we treated RosaiDTR/CD11c-cre and control mice with DT only from day 4 of P. yoelii infection onward. Strikingly, this approach had no impact on the activation and IFN-γ production of CD4⁺ and CD8⁺ effector T cells. These results indicate that CD11c^high DCs play a crucial role in eliciting effector T cell responses during the initial phase, but are dispensable during ongoing infection with P. yoelii.