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Sci Rep. 2015 Oct 6;5:14802. doi: 10.1038/srep14802.

Mammalian Host-Versus-Phage immune response determines phage fate in vivo.

Author information

1
Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
2
Institute of Computer Science, Wrocław University of Technology, Wyb. Wyspiańskiego 27, 50-370, Wrocław, Poland.
3
USI, Unit of Nanostructural Bio-Interactions, Department of Immunology of Infectious Diseases, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.

Abstract

Emerging bacterial antibiotic resistance draws attention to bacteriophages as a therapeutic alternative to treat bacterial infection. Examples of phage that combat bacteria abound. However, despite careful testing of antibacterial activity in vitro, failures nevertheless commonly occur. We investigated immunological response of phage antibacterial potency in vivo. Anti-phage activity of phagocytes, antibodies, and serum complement were identified by direct testing and by high-resolution fluorescent microscopy. We accommodated the experimental data into a mathematical model. We propose a universal schema of innate and adaptive immunity impact on phage pharmacokinetics, based on the results of our numerical simulations. We found that the mammalian-host response to infecting bacteria causes the concomitant removal of phage from the system. We propose the notion that this effect as an indirect pathway of phage inhibition by bacteria with significant relevance for the clinical outcome of phage therapy.

PMID:
26440922
PMCID:
PMC4594097
DOI:
10.1038/srep14802
[Indexed for MEDLINE]
Free PMC Article

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