Induction of a homeostatic circuit in lung tissue by microbial compounds

Immunity. 2006 Apr;24(4):475-87. doi: 10.1016/j.immuni.2006.02.008.


TGFbeta presented and activated by integrin alphavbeta6 expressed on alveolar epithelial cells (AEC) continuously inhibits the functionality of alveolar macrophages (AM). Despite this inhibition, AM retain their ability to respond to inhaled microorganisms. Herein we describe a homeostatic circuit through which the effects of microbial products on macrophages transiently circumvent this inhibition by repressing alphavbeta6 expression on AEC. Subsequent production of matrix metalloproteinases by activated AM activates latent TGFbeta, reinduces alphavbeta6 expression, and thereby reinstates tonic inhibition of AM function. Our results reveal how AM can be activated while minimizing their potential to inflict collateral damage to the adjacent lung tissue and indicate that tissue-specific microenvironmental factors shape organ-specific defense strategies against microbial invasion.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Bacterial Infections / immunology*
  • Blotting, Western
  • Cell Communication / immunology*
  • Female
  • Homeostasis / immunology*
  • Integrins / immunology
  • Integrins / metabolism
  • Lung / cytology
  • Lung / immunology*
  • Lung / microbiology
  • Macrophages, Alveolar / immunology*
  • Matrix Metalloproteinases / immunology
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Receptor Cross-Talk / immunology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / microbiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism


  • Antigens, Neoplasm
  • Integrins
  • Toll-Like Receptors
  • Transforming Growth Factor beta
  • integrin alphavbeta6
  • Matrix Metalloproteinases