scholarly journals Rhinovirus Infection Induces Degradation of Antimicrobial Peptides and Secondary Bacterial Infection in Chronic Obstructive Pulmonary Disease

2012 ◽  
Vol 186 (11) ◽  
pp. 1117-1124 ◽  
Author(s):  
Patrick Mallia ◽  
Joseph Footitt ◽  
Rosa Sotero ◽  
Annette Jepson ◽  
Marco Contoli ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Antimicrobial Peptides ◽  
Bacterial Infection ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Secondary Bacterial Infection ◽  
Rhinovirus Infection

scholarly journals Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease

2019 ◽  
Vol 11 (507) ◽  
pp. eaav3879 ◽  
Author(s):  
Aran Singanayagam ◽  
Nicholas Glanville ◽  
Leah Cuthbertson ◽  
Nathan W. Bartlett ◽  
Lydia J. Finney ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Bacterial Infection ◽  
Pulmonary Disease ◽  
Cathepsin D ◽  
Inhaled Corticosteroids ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Airway Diseases ◽  
Infection Susceptibility ◽  
Pulmonary Immunity

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 withStreptococcus 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.

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