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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / metabolism*
  • Bacterial Infections / etiology*
  • Bacterial Infections / metabolism*
  • Bacterial Load
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Disease Models, Animal
  • Interleukin-12 / biosynthesis
  • Interleukin-12 Subunit p40 / blood
  • Lectins, C-Type / metabolism*
  • Lymphocyte Activation / immunology*
  • Lymphocyte Depletion
  • Male
  • Mannose-Binding Lectins / metabolism*
  • Mice
  • Mycobacterium bovis / immunology
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / microbiology
  • Spleen / pathology
  • T-Cell Antigen Receptor Specificity

Substances

  • Antigens, Surface
  • Cd207 protein, mouse
  • Interleukin-12 Subunit p40
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Interleukin-12