image_1_Langerin+ CD8α+ Dendritic Cells Drive Early CD8+ T Cell Activation and IL-12 Production During Systemic Bacterial Infection.TIF PrendergastKelly A. DanielsNaomi J. R. PetersenTroels HermansIan F. R. KirmanJoanna 2018 <p>Bloodstream infections induce considerable morbidity, high mortality, and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteremia is incomplete. Langerin<sup>+</sup> CD8α<sup>+</sup> dendritic cells (DCs), residing in the marginal zone of the murine spleen, have the capacity to cross-prime CD8<sup>+</sup> T cells and produce IL-12, both of which are important components of antimicrobial immunity. Accordingly, we hypothesized that this DC subset may be a key promoter of adaptive immune responses to blood-borne bacterial infections. Utilizing mice that express the diphtheria toxin receptor under control of the langerin promoter, we investigated the impact of depleting langerin<sup>+</sup> CD8α<sup>+</sup> DCs in a murine model of intravenous infection with Mycobacterium bovis bacille Calmette–Guerin (BCG). In the absence of langerin<sup>+</sup> CD8α<sup>+</sup> DCs, the immune response to blood-borne BCG infection was diminished: bacterial numbers in the spleen increased, serum IL-12p40 decreased, and delayed CD8<sup>+</sup> T cell activation, proliferation, and IFN-γ production was evident. Our data revealed that langerin<sup>+</sup> CD8α<sup>+</sup> DCs play a pivotal role in initiating CD8<sup>+</sup> T cell responses and IL-12 production in response to bacteremia and may influence the early control of systemic bacterial infections.</p>