Aspergillosis and the role of mucins in cystic fibrosis

Pediatr Pulmonol. 2017 Apr;52(4):548-555. doi: 10.1002/ppul.23618. Epub 2016 Nov 21.

Abstract

The prevalence of aspergillosis in CF patients has until recently been underestimated, but increasing evidence suggests that it may play an important role in the progression of CF lung disease. In healthy airways, Aspergillus fumigatus can be efficiently removed from the lung by mechanisms such as mucociliary clearance and cough. However, these mechanisms are defective in CF, allowing pathogens such as A. fumigatus to germinate and establish chronic infections within the airways. The precise means by which A. fumigatus contributes to CF lung disease remain largely unclear. As the first point of contact within the lung, and an important component of the innate immune system, it is likely that the mucus barrier plays an important role in this process. Study of the functional interplay between this vital protective barrier, and in particular its principal structural components, the polymeric gel-forming mucins, and CF pathogens such as A. fumigatus, is at an early stage. A. fumigatus protease activity has been shown to upregulate mucus production by inducing mucin mRNA and protein expression, and A. fumigatus proteases and glycosidases are able to degrade mucins. This may allow A. fumigatus to alter mucus barrier properties to promote fungal colonization of the airways and/or utilize mucins as a nutrient source. Moreover, conidial surface lectin binding to mucin glycans is a key aspect of clearance of Aspergillus from the lung in health but may be an important aspect of colonization, where mucociliary clearance is compromised, as in the CF lung. Here we discuss the nature of the mucus barrier and its mucin components in CF, and how they may be implicated in A. fumigatus infection. Pediatr Pulmonol 2017;52:548-555. © 2016 The Authors. Pediatric Pulmonology. Published by Wiley Periodicals, Inc.

Keywords: Aspergillus fumigatus; cystic fibrosis; mucins; mucus.

Publication types

  • Review

MeSH terms

  • Aspergillosis / complications*
  • Aspergillosis / microbiology
  • Aspergillus fumigatus / isolation & purification*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / microbiology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Humans

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator