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

Autor: Zamora PF; Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Hanover, New Hampshire, United States of America., Reidy TG; Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America., Armbruster CR; Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Hanover, New Hampshire, United States of America.; Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America., Sun M; Center for Biological Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America., Van Tyne D; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America., Turner PE; Center for Phage Biology and Therapy, Yale University, New Haven, Connecticut, United States of America.; Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut, United States of America.; Program in Microbiology, Yale School of Medicine, New Haven, Connecticut, United States of America.; Quantitative Biology Institute, Yale University, New Haven, Connecticut, United States of America., Koff JL; Center for Phage Biology and Therapy, Yale University, New Haven, Connecticut, United States of America.; Department of Medicine, Yale University, New Haven, Connecticut, United States of America., Bomberger JM; Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Hanover, New Hampshire, United States of America.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2024 Apr 23; Vol. 22 (4), pp. e3002566. Date of Electronic Publication: 2024 Apr 23 (Print Publication: 2024).
DOI: 10.1371/journal.pbio.3002566
Abstrakt: 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.
Competing Interests: PET is cofounder of Felix Biotechnology, Inc., a company that seeks to develop phages for human therapy. Yale University has an institutional conflict of interest related to this project (PET & JLK). Yale may receive financial benefit related to the therapy used in this protocol.
(Copyright: © 2024 Zamora et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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