Anti-microbial immunity is impaired in COPD patients with frequent exacerbations

Aran Singanayagam; Su-Ling Loo; Maria Calderazzo; Lydia J Finney; Maria-Belen Trujillo Torralbo; Eteri Bakhsoliani; Jason Girkin; Punnam Veerati; Prabuddha S Pathinayake; Kristy S Nichol; Andrew Reid; Joseph Foottit; Sebastian L Johnston; Nathan W Bartlett; Patrick Mallia

Despite observing impaired ex vivo RV-induction of IFN and ISG mRNA in frequent exacerbator BECs at 72 hours post-infection, we did not observe corresponding differences in protein production of type I and III IFNs by these cells at the same timepoint. Our studies were limited by sample availability only allowing evaluation at a single timepoint. We have previously reported that protein production of IFN persists at least up to 96 hours in this cell type 21 and it is feasible that evaluation at later timepoints may be required to observe significant differences in translated IFN proteins. Despite a lack of difference in absolute levels of IFN protein, the reduced ISG expression observed in frequent exacerbators supports a less effective IFN-induced response in these subjects Bacterial infection is also associated with exacerbation in COPD with increased PCR-based bacterial detection at exacerbation versus stable state suggesting a causative role 28, 29 . Additionally, virusinduced secondary bacterial infection has been reported in both experimental and naturally occurring exacerbations 12, 13 . We have previously reported that experimental RV challenge in patients with COPD is associated with increased frequency of secondary bacterial infection compared to healthy subjects 12,30 via a mechanism of neutrophil elastase-mediated cleavage of anti-microbial peptides SLPI and elafin 12 . Here, we extend these findings to reveal that frequent exacerbators have higher bacterial loads at 2 weeks following onset of virus-associated exacerbation, suggesting that this subgroup of COPD patients might be at greatest risk of developing secondary bacterial infection following initial virus infection. Although we found no difference in levels of SLPI and elafin according to exacerbation frequency, we did identify that expression of another AMP MBL-2 was reduced in frequent author/funder. All rights reserved. No reuse allowed without permission.