Plasmacytoid dendritic cells play a role for effective innate immune responses during Chlamydia pneumoniae infection in mice

PLoS One. 2012;7(10):e48655. doi: 10.1371/journal.pone.0048655. Epub 2012 Oct 31.

Abstract

Plasmacytoid dendritic cells (pDCs) are known for their robust antiviral response and their pro-tolerance effects towards allergic diseases and tissue engraftments. However, little is known about the role pDCs may play during a bacterial infection, including pulmonary Chlamydia pneumoniae (CP). In this study, we investigated the role of pDCs during pulmonary CP infection. Our results revealed that depletion of pDCs during acute CP infection in mice results in delayed and reduced lung inflammation, with an early delay in cellular recruitment and significant reduction in early cytokine production in the lungs. This was followed by impaired and delayed bacterial clearance from the lungs which then resulted in a severe and prolonged chronic inflammation and iBALT like structures containing large numbers of B and T cells in these animals. We also observed that increasing the pDC numbers in the lung by FLT3L treatment experimentally results in greater lung inflammation during acute CP infection. In contrast to these results, restimulation of T-cells in the draining lymph nodes of pDC-depleted mice induced greater amounts of proinflammatory cytokines than we observed in control mice. These results suggest that pDCs in the lung may provide critical proinflammatory innate immune responses in response to CP infection, but are suppressive towards adaptive immune responses in the lymph node. Thus pDCs in the lung and the draining lymph node appear to have different roles and phenotypes during acute CP infection and may play a role in host immune responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoalveolar Lavage Fluid / microbiology
  • Cell Line, Tumor
  • Chlamydial Pneumonia / immunology*
  • Chlamydial Pneumonia / microbiology
  • Chlamydophila pneumoniae / immunology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Diphtheria Toxin / immunology
  • Diphtheria Toxin / pharmacology
  • Female
  • Flow Cytometry
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Immunity, Innate / immunology*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / immunology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Ligands
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / microbiology
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Diphtheria Toxin
  • HBEGF protein, human
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-6
  • Ligands
  • Membrane Proteins
  • flt3 ligand protein
  • Interferon-gamma