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CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis

Abdullah A Tarique1, Peter D Sly2, Patrick G Holt3

  • 1Child Health Research Centre, The University of Queensland, Brisbane, Australia.

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society
|April 22, 2017
PubMed
Abstract

Insights

Macrophages in cystic fibrosis (CF) lung disease show abnormal M2 activation due to faulty cystic fibrosis trans-membrane conductance regulator (CFTR) function, contributing to inflammation.

Area of Science:

  • Immunology
  • Respiratory Medicine
  • Cell Biology

Background:

  • The role of macrophages in cystic fibrosis (CF) lung disease is understudied.
  • Macrophages, particularly alternatively activated M2 macrophages, are hypothesized to be abnormal in CF.

Purpose of the Study:

  • To investigate the phenotype and function of M1 and M2 macrophages in adults and children with CF.
  • To determine if cystic fibrosis trans-membrane conductance regulator (CFTR) influences macrophage polarization and function.

Main Methods:

  • Blood samples were collected from CF patients (adults and children) during acute exacerbation and stable states.
  • Monocytes were differentiated into macrophages and polarized into M1 and M2 phenotypes ex-vivo.
  • Macrophage function was assessed and compared to healthy controls.

Main Results:

  • Macrophages from CF patients failed to polarize to the M2 phenotype in the absence of functional CFTR.
  • This M2 polarization failure is linked to a post-transcriptional defect in IL-13Rα1 production and expression.
  • M1 polarization remained unaffected by CFTR status.

Conclusions:

  • An imbalance in macrophage phenotypes and functions, dependent on CFTR, may contribute to heightened inflammation in CF lung disease.
  • Dysfunctional M2 macrophages could play a significant role in CF pathogenesis.
Keywords:
Alternatively activated macrophages)CFTRCFTR inhibitorsClassically activated macrophagesCystic fibrosis (CF)EndocytosisIL-13 receptorMonocyte-derived macrophagesPhagocytosis

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