Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells.

Phage therapy is a therapeutic approach to treat multidrug-resistant (MDR) infections that employs lytic bacteriophages (phages) to eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there is scarce data regarding its effects on the human host. H...

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Main Authors: Paula F Zamora, Thomas G Reidy, Catherine R Armbruster, Ming Sun, Daria Van Tyne, Paul E Turner, Jonathan L Koff, Jennifer M Bomberger
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-04-01
Series:PLoS Biology
Online Access:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002566&type=printable
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author Paula F Zamora
Thomas G Reidy
Catherine R Armbruster
Ming Sun
Daria Van Tyne
Paul E Turner
Jonathan L Koff
Jennifer M Bomberger
author_facet Paula F Zamora
Thomas G Reidy
Catherine R Armbruster
Ming Sun
Daria Van Tyne
Paul E Turner
Jonathan L Koff
Jennifer M Bomberger
author_sort Paula F Zamora
collection DOAJ
description Phage therapy is a therapeutic approach to treat multidrug-resistant (MDR) infections that employs lytic bacteriophages (phages) to eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there is scarce data regarding its effects on the human host. Here, we aimed to understand how lytic phages interact with cells of the airway epithelium, the tissue site that is colonized by bacterial biofilms in numerous chronic respiratory disorders. Using a panel of Pseudomonas aeruginosa phages and human airway epithelial cells (AECs) derived from a person with cystic fibrosis (CF), we determined that interactions between phages and epithelial cells depend on specific phage properties as well as physiochemical features of the microenvironment. Although poor at internalizing phages, the airway epithelium responds to phage exposure by changing its transcriptional profile and secreting antiviral and proinflammatory cytokines that correlate with specific phage families. Overall, our findings indicate that mammalian responses to phages are heterogenous and could potentially alter the way that respiratory local defenses aid in bacterial clearance during phage therapy. Thus, besides phage receptor specificity in a particular bacterial isolate, the criteria to select lytic phages for therapy should be expanded to include mammalian cell responses.
format Article
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institution Kabale University
issn 1544-9173
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language English
publishDate 2024-04-01
publisher Public Library of Science (PLoS)
record_format Article
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spelling doaj-art-6a64dc52ab974e2cb54129ada93e708c2025-08-20T03:41:46ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-04-01224e300256610.1371/journal.pbio.3002566Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells.Paula F ZamoraThomas G ReidyCatherine R ArmbrusterMing SunDaria Van TynePaul E TurnerJonathan L KoffJennifer M BombergerPhage therapy is a therapeutic approach to treat multidrug-resistant (MDR) infections that employs lytic bacteriophages (phages) to eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there is scarce data regarding its effects on the human host. Here, we aimed to understand how lytic phages interact with cells of the airway epithelium, the tissue site that is colonized by bacterial biofilms in numerous chronic respiratory disorders. Using a panel of Pseudomonas aeruginosa phages and human airway epithelial cells (AECs) derived from a person with cystic fibrosis (CF), we determined that interactions between phages and epithelial cells depend on specific phage properties as well as physiochemical features of the microenvironment. Although poor at internalizing phages, the airway epithelium responds to phage exposure by changing its transcriptional profile and secreting antiviral and proinflammatory cytokines that correlate with specific phage families. Overall, our findings indicate that mammalian responses to phages are heterogenous and could potentially alter the way that respiratory local defenses aid in bacterial clearance during phage therapy. Thus, besides phage receptor specificity in a particular bacterial isolate, the criteria to select lytic phages for therapy should be expanded to include mammalian cell responses.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002566&type=printable
spellingShingle Paula F Zamora
Thomas G Reidy
Catherine R Armbruster
Ming Sun
Daria Van Tyne
Paul E Turner
Jonathan L Koff
Jennifer M Bomberger
Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells.
PLoS Biology
title Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells.
title_full Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells.
title_fullStr Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells.
title_full_unstemmed Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells.
title_short Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells.
title_sort lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells
url https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002566&type=printable
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