Bacteriophage uptake by mammalian cell layers represents a potential sink that may impact phage therapy.
Immunology
Microbiology
Virology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
23 Apr 2021
23 Apr 2021
Historique:
received:
30
11
2020
revised:
15
02
2021
accepted:
04
03
2021
entrez:
15
4
2021
pubmed:
16
4
2021
medline:
16
4
2021
Statut:
epublish
Résumé
It is increasingly apparent that bacteriophages, viruses that infect bacteria and more commonly referred to as simply phages, have tropisms outside their bacterial hosts. Using live tissue culture cell imaging, we demonstrate that cell type, phage size, and morphology play a major role in phage internalization. Uptake was validated under physiological conditions using a microfluidic device. Phages adhered to mammalian tissues, with adherent phages being subsequently internalized by macropinocytosis, with functional phages accumulating intracellularly. We incorporated these results into a pharmacokinetic model demonstrating the potential impact of phage accumulation by cell layers, which represents a potential sink for circulating phages in the body. During phage therapy, high doses of phages are directly administered to a patient in order to treat a bacterial infection, thereby facilitating broad interactions between phages and mammalian cells. Understanding these interactions will have important implications on innate immune responses, phage pharmacokinetics, and the efficacy of phage therapy.
Identifiants
pubmed: 33855278
doi: 10.1016/j.isci.2021.102287
pii: S2589-0042(21)00255-8
pmc: PMC8024918
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102287Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
J.J.B. has a patent application related to this work (WO2018129536A1).
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