title: Mammalian Host-Versus-Phage immune response determines phage fate in vivo.
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.
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Hodyra-Stefaniak
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Miernikiewicz
authors.affiliation: Institute of Computer Science, Wrocław University of Technology, Wyb. Wyspiańskiego 27, 50-370, Wrocław, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Drapała
authors.affiliation: 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.
authors.forename: Marek
authors.initials: M
authors.lastname: Drab
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jończyk-Matysiak
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Lecion
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Kaźmierczak
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Beta
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Majewska
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Harhala
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bubak
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kłopot
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Górski
authors.affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Dąbrowska
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology / Q000821:virology; D008297:Male; D008322:Mammals / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods; D008962:Models, Theoretical; D010587:Phagocytosis; D017105:Pseudomonas Phages / Q000276:immunology / Q000502:physiology*; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000821:virology
chemical_list: D008070:Lipopolysaccharides