Human β-defensin-2 production upon viral and bacterial co-infection is attenuated in COPD.

Autor:	Arnason JW; Department of Medicine, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Murphy JC; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Kooi C; Department of Medicine, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Wiehler S; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Traves SL; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Shelfoon C; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Maciejewski B; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Dumonceaux CJ; Department of Medicine, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Lewenza WS; Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Proud D; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Leigh R; Department of Medicine, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.; Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2017 May 10; Vol. 12 (5), pp. e0175963. Date of Electronic Publication: 2017 May 10 (Print Publication: 2017).
DOI:	10.1371/journal.pone.0175963
Abstrakt:	Viral-bacterial co-infections are associated with severe exacerbations of COPD. Epithelial antimicrobial peptides, including human β-defensin-2 (HBD-2), are integral to innate host defenses. In this study, we examined how co-infection of airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD-2 expression, and whether these responses are attenuated by cigarette smoke and in epithelial cells obtained by bronchial brushings from smokers with normal lung function or from COPD patients. When human airway epithelial cells from normal lungs were infected with rhinovirus, Pseudomonas aeruginosa, or the combination, co-infection with rhinovirus and bacteria resulted in synergistic induction of HBD-2 (p<0.05). The combination of virus and flagellin replicated this synergistic increase (p<0.05), and synergy was not seen using a flagella-deficient mutant Pseudomonas (p<0.05). The effects of Pseudomonas aeruginosa were mediated via interactions of flagellin with TLR5. The effects of HRV-16 depended upon viral replication but did not appear to be mediated via the intracellular RNA helicases, retinoic acid-inducible gene-I or melanoma differentiation-associated gene-5. Cigarette smoke extract significantly decreased HBD-2 production in response to co-infection. Attenuated production was also observed following co-infection of cells obtained from healthy smokers or COPD patients compared to healthy controls (p<0.05). We conclude that co-exposure to HRV-16 and Pseudomonas aeruginosa induces synergistic production of HBD-2 from epithelial cells and that this synergistic induction of HBD-2 is reduced in COPD patients. This may contribute to the more severe exacerbations these patients experience in response to viral-bacterial co-infections.
Databáze:	MEDLINE
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