BibTex format
@article{Singanayagam:2019:10.1126/scitranslmed.aav3879,
author = {Singanayagam, A and Glanville, N and Cuthbertson, L and Bartlett, NW and Finney, LJ and Turek, E and Bakhsoliani, E and Calderazzo, MA and Trujillo-Torralbo, M-B and Footitt, J and James, PL and Fenwick, P and Kemp, SV and Clarke, TB and Wedzicha, JA and Edwards, MR and Moffatt, M and Cookson, WO and Mallia, P and Johnston, SL},
doi = {10.1126/scitranslmed.aav3879},
journal = {Science Translational Medicine},
pages = {1--13},
title = {Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease},
url = {http://dx.doi.org/10.1126/scitranslmed.aav3879},
volume = {11},
year = {2019}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Bacterial infection commonly complicates inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD). The mechanisms of increased infection susceptibility and how use of the commonly prescribed therapy inhaled corticosteroids (ICS) accentuates pneumonia risk in COPD are poorly understood. Here, using analysis of samples from patients with COPD, we show that ICS use is associated with lung microbiota disruption leading to proliferation of streptococcal genera, an effect that could be recapitulated in ICS-treated mice. To study mechanisms underlying this effect, we used cellular and mouse models of streptococcal expansion with Streptococcus pneumoniae, an important pathogen in COPD, to demonstrate that ICS impairs pulmonary clearance of bacteria through suppression of the antimicrobial peptide cathelicidin. ICS impairment of pulmonary immunity was dependent on suppression of cathelicidin because ICS had no effect on bacterial loads in mice lacking cathelicidin (Camp-/-) and exogenous cathelicidin prevented ICS-mediated expansion of streptococci within the microbiota and improved bacterial clearance. Suppression of pulmonary immunity by ICS was mediated by augmentation of the protease cathepsin D. Collectively, these data suggest a central role for cathepsin D/cathelicidin in the suppression of antibacterial host defense by ICS in COPD. Therapeutic restoration of cathelicidin to boost antibacterial immunity and beneficially modulate the lung microbiota might be an effective strategy in COPD.
AU - Singanayagam,A
AU - Glanville,N
AU - Cuthbertson,L
AU - Bartlett,NW
AU - Finney,LJ
AU - Turek,E
AU - Bakhsoliani,E
AU - Calderazzo,MA
AU - Trujillo-Torralbo,M-B
AU - Footitt,J
AU - James,PL
AU - Fenwick,P
AU - Kemp,SV
AU - Clarke,TB
AU - Wedzicha,JA
AU - Edwards,MR
AU - Moffatt,M
AU - Cookson,WO
AU - Mallia,P
AU - Johnston,SL
DO - 10.1126/scitranslmed.aav3879
EP - 13
PY - 2019///
SN - 1946-6234
SP - 1
TI - Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease
T2 - Science Translational Medicine
UR - http://dx.doi.org/10.1126/scitranslmed.aav3879
UR - https://www.ncbi.nlm.nih.gov/pubmed/31462509
UR - https://stm.sciencemag.org/content/11/507/eaav3879
UR - http://hdl.handle.net/10044/1/74112
VL - 11
ER -