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Front Immunol. 2018 May 7;9:953. doi: 10.3389/fimmu.2018.00953. eCollection 2018.

Langerin+ CD8α+ Dendritic Cells Drive Early CD8+ T Cell Activation and IL-12 Production During Systemic Bacterial Infection.

Author information

1
Malaghan Institute of Medical Research, Wellington, New Zealand.
2
School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
3
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
4
Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand.

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+ CD8α+ 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+ CD8α+ DCs in a murine model of intravenous infection with Mycobacterium bovis bacille Calmette-Guerin (BCG). In the absence of langerin+ CD8α+ 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-γ production was evident. Our data revealed that langerin+ CD8α+ 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.

KEYWORDS:

bacille Calmette–Guerin; dendritic cell; diphtheria toxin; langerin; systemic infection

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