Abstract
Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may play a role in progressive lung disease. As cystic fibrosis transmembrane conductance regulator is expressed in cells of the innate immune system, we hypothesised that impaired antifungal immune responses play a role in CF-related Aspergillus lung disease.
Peripheral blood mononuclear cells, polymorphonuclear cells (PMN) and monocytes were isolated from blood samples taken from CF patients and healthy volunteers. Live-cell imaging and colorimetric assays were used to assess antifungal activity in vitro. Production of reactive oxygen species (ROS) was measured using luminol-induced chemiluminescence and was related to clinical metrics as collected by case report forms.
CF phagocytes are as effective as those from healthy controls with regards to phagocytosis, killing and restricting germination of A. fumigatus conidia. ROS production by CF phagocytes was up to four-fold greater than healthy controls (p<0.05). This effect could not be replicated in healthy phagocytes by priming with lipopolysaccharide or serum from CF donors. Increased production of ROS against A. fumigatus by CF PMN was associated with an increased number of clinical exacerbations in the previous year (p=0.007) and reduced lung function (by forced expiratory volume in 1 s) (p=0.014).
CF phagocytes mount an intrinsic exaggerated release of ROS upon A. fumigatus stimulation which is associated with clinical disease severity.
Abstract
Excessive superoxide production by CF phagocytes against A. fumigatus is associated with clinical disease severity http://ow.ly/Elwy30i8mLe
Footnotes
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Author contributions: A. Warris and G. Devereaux conceived and designed this study; S.F. Brunel and J.A. Willment designed and performed the study; A. Warris, G. Devereaux, S.F. Brunel and G.D. Brown analysed and interpreted the data; and all authors drafted the manuscript for intellectual content.
Conflict of interest: A. Warris reports receiving grants and personal fees from Gilead, and personal fees from Basilea, outside the submitted work.
Support statement: A. Warris, G.D. Brown, S.F. Brunel and J.A. Willment were supported by the Wellcome Trust Strategic Award (grant 097377) and the MRC Centre for Medical Mycology (grant MR/N006364/1) at the University of Aberdeen. A. Warris and S.F. Brunel were also supported by the Chloe Fund. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 3, 2017.
- Accepted January 26, 2018.
- Copyright ©ERS 2018
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