Current concepts: host-pathogen interactions in cystic fibrosis airways disease

Abstract

Chronic infection and inflammation are defining characteristics of cystic fibrosis (CF) airway disease. Conditions within the airways of patients living with CF are conducive to colonisation by a variety of opportunistic bacterial, viral and fungal pathogens. Improved molecular identification of microorganisms has begun to emphasise the polymicrobial nature of infections in the CF airway microenvironment. Changes to CF airway physiology through loss of cystic fibrosis transmembrane conductance regulator functionality result in a wide range of immune dysfunctions, which permit pathogen colonisation and persistence. This review will summarise the current understanding of how CF pathogens infect, interact with and evade the CF host.

Figure 1.

Host–pathogen interactions in cystic fibrosis (CF). This figure illustrates a few of the various interactions between bacterial, viral and fungal pathogens and the CF host. a) Chronically infecting strains of Pseudomonas aeruginosa frequently acquire hypermutable phenotypes through mismatch repair deficiency, encouraging antibiotic resistance and adapted virulence. Inflammatory responses are modulated through changes in lipid A structure and flagellin expression. This provides resistance to host antimicrobial peptides (AMP) and alters CXCL8 production through Toll-like receptor (TLR)4. Loss of motility/changes in flagellin expression can occur in order to evade recognition by TLR5 and phagocytosis by alveolar macrophages. The presence of flagellin can also induce development of myeloid-derived suppressor cells (MDSCs) leading to suppression of T-cell responses. b) Rhinoviral infection may increase expression of cellular adhesion molecules, such as carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), and enhance attachment of bacterial pathogens to host cells. c) Decreased uptake of Aspergillus fumigatus conidia by cystic fibrosis transmembrane conductance regulator (CFTR)-deficient epithelial cells results in reduced clearance and increased cell death. Germination from spore to hyphal form results in increased inflammatory responses. Bronchial epithelial cells induce T-cell-mediated T-helper cell (Th)2 and Th17 responses complicit in allergic bronchopulmonary aspergillosis. This may be further enhanced by A. fumigatus mediated downregulation of the vitamin D receptor (VDR) and increased interleukin (IL)-5/IL-13 production by gliotoxin.