Bacterial-induced protection against allergic inflammation through a multicomponent immunoregulatory mechanism

Thorax. 2011 Sep;66(9):755-63. doi: 10.1136/thx.2010.152512. Epub 2011 Mar 21.

Abstract

Background: Airborne microbial products have been reported to promote immune responses that suppress asthma, yet how these beneficial effects take place remains controversial and poorly understood.

Methods: We exposed mice to the bacterium Escherichia coli and subsequently induced allergic airway inflammation through sensitization and intranasal challenge with ovalbumin.

Results: Pulmonary exposure to the bacterium Escherichia coli leads to a suppression of allergic airway inflammation. This immune modulation was neither mediated by the induction of a T helper 1 (Th1) response nor regulatory T cells; however, it was dependent on Toll-like receptor 4 (TLR4) but did not involve TLR desensitisation. Dendritic cell migration to the draining lymph nodes and activation of T cells was unaffected by prior exposure to E. coli, while dendritic cells in the lung displayed a less activated phenotype and had impaired antigen presentation capacity. Consequently, in situ Th2 cytokine production was abrogated. The suppression of airway hyper-responsiveness was mediated through the recruitment of gd T cells; however, the suppression of dendritic cells and T cells was mediated through a distinct mechanism that could not be overcome by the local administration of activated dendritic cells, or by the in vivo administration of tumour necrosis factor a.

Conclusion: Our data reveal a localized immunoregulatory pathway that acts to protect the airways from allergic inflammation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology
  • Asthma / pathology
  • Asthma / prevention & control*
  • Bacterial Outer Membrane Proteins / immunology
  • Bacterial Outer Membrane Proteins / metabolism
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Escherichia coli / immunology*
  • Escherichia coli / isolation & purification
  • Escherichia coli / metabolism
  • Flow Cytometry
  • Immunomodulation / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Th2 Cells / immunology*

Substances

  • Bacterial Outer Membrane Proteins
  • TLR protein, bacteria