Plasmacytoid dendritic cell depletion modifies FoxP3+ T cell homeostasis and the clinical course of bacterial pneumonia in mice

J Leukoc Biol. 2019 Oct;106(4):977-985. doi: 10.1002/JLB.3AB0119-014RR. Epub 2019 Jul 2.

Abstract

Plasmacytoid dendritic cells (pDC) are critical to antiviral defense because of their high production of type I IFNs; less is known regarding their functions in bacterial infection. Moreover, pDC are involved in immunomodulation. A stable pool of regulatory T cells (Treg) is crucial for maintaining immune homeostasis. However, interactions between pDC and Treg regarding the regulation of Treg homeostasis are understudied. By using BDCA2-DTR mice as a systemic pDC depletion model, we identified increased steady-state numbers of FoxP3+ T cells with an effector Treg-like phenotype in lungs, liver, and spleen tissues. During sublethal, pulmonary Klebsiella pneumoniae infection, pDC deficiency also elevated respiratory FoxP3+ T cell numbers. Additionally, the improvement in acute pneumonia survival until day 5 post infection was accompanied by impaired proinflammatory cytokine production. In contrast, pDC-depleted mice exhibited a delayed clinical recovery during the post-acute phase. Therefore, we assume that pDC act as immunomodulators supporting the rapid onset of immune response in a proinflammatory manner and regulate inflammation or tissue regeneration in the post-acute phase. In summary, pDC assist in FoxP3+ T cell homeostasis and the regulation of Klebsiella-pneumonia progression.

Keywords: BDCA2-DTR mice; Klebsiella pneumoniae; bacterial infection; immunomodulation; inflammation; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Biomarkers / metabolism
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Forkhead Transcription Factors / metabolism*
  • Homeostasis*
  • Inflammation Mediators / metabolism
  • Klebsiella pneumoniae / physiology
  • Lectins, C-Type / metabolism
  • Lung / immunology
  • Lung / pathology
  • Mice, Inbred C57BL
  • Pneumonia, Bacterial / immunology*
  • Pneumonia, Bacterial / microbiology*
  • Pneumonia, Bacterial / pathology
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Biomarkers
  • CD69 antigen
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Inflammation Mediators
  • Lectins, C-Type