Langerin⁺ CD8?⁺ Dendritic Cells Drive Early CD8⁺ T Cell Activation and IL-12 Production During Systemic Bacterial Infection.

ABSTRACT: 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⁺ CD8?⁺ dendritic cells (DCs), residing in the marginal zone of the murine spleen, have the capacity to cross-prime CD8⁺ 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⁺ CD8?⁺ DCs in a murine model of intravenous infection with Mycobacterium bovis bacille Calmette-Guerin (BCG). In the absence of langerin⁺ CD8?⁺ DCs, the immune response to blood-borne BCG infection was diminished: bacterial numbers in the spleen increased, serum IL-12p40 decreased, and delayed CD8⁺ T cell activation, proliferation, and IFN-? production was evident. Our data revealed that langerin⁺ CD8?⁺ DCs play a pivotal role in initiating CD8⁺ T cell responses and IL-12 production in response to bacteremia and may influence the early control of systemic bacterial infections.

SUBMITTER: Prendergast KA 

PROVIDER: S-EPMC5949331 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature