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

Hodyra-Stefaniak K, Miernikiewicz P, Drapała J, Drab M, Jończyk-Matysiak E, Lecion D, Kaźmierczak Z, Beta W, Majewska J, Harhala M, Bubak B, Kłopot A, Górski A, Dąbrowska K - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, 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.

No MeSH data available.


Related in: MedlinePlus

Dynamics involving bacteria, phage, and mammalian immunity in vivo.All symbols used in this schema have been applied as variables or parameters in equations of a mathematical model developed for studies of these interactions (see: Materials and Methods) P – bacteriophages, S – bacteria, I – innate immunity, A – adaptive immunity to phages, B – adaptive immunity to bacteria. Red arrows represent a stimulatory while blue arrows represent an inhibitory effect.
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f3: Dynamics involving bacteria, phage, and mammalian immunity in vivo.All symbols used in this schema have been applied as variables or parameters in equations of a mathematical model developed for studies of these interactions (see: Materials and Methods) P – bacteriophages, S – bacteria, I – innate immunity, A – adaptive immunity to phages, B – adaptive immunity to bacteria. Red arrows represent a stimulatory while blue arrows represent an inhibitory effect.

Mentions: Experimental data described above together with previous findings in the field92728 were integrated into a general schema of tripartite interactions between bacteriophages, mammalian immunity and bacteria (Fig. 3) The schema summarizes main reciprocal dependencies, specifically limiting or inducing effects. The key assumptions for this schema were as follows (Fig. 3): first, adaptive immunity specific to phages and adaptive immunity specific to bacteria have no important cross-talk; second, phages are not able to boost innate immunity2728; third, boosted innate immunity acts against bacteria, but at the same time it also acts against the phage.


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

Hodyra-Stefaniak K, Miernikiewicz P, Drapała J, Drab M, Jończyk-Matysiak E, Lecion D, Kaźmierczak Z, Beta W, Majewska J, Harhala M, Bubak B, Kłopot A, Górski A, Dąbrowska K - Sci Rep (2015)

Dynamics involving bacteria, phage, and mammalian immunity in vivo.All symbols used in this schema have been applied as variables or parameters in equations of a mathematical model developed for studies of these interactions (see: Materials and Methods) P – bacteriophages, S – bacteria, I – innate immunity, A – adaptive immunity to phages, B – adaptive immunity to bacteria. Red arrows represent a stimulatory while blue arrows represent an inhibitory effect.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4594097&req=5

f3: Dynamics involving bacteria, phage, and mammalian immunity in vivo.All symbols used in this schema have been applied as variables or parameters in equations of a mathematical model developed for studies of these interactions (see: Materials and Methods) P – bacteriophages, S – bacteria, I – innate immunity, A – adaptive immunity to phages, B – adaptive immunity to bacteria. Red arrows represent a stimulatory while blue arrows represent an inhibitory effect.
Mentions: Experimental data described above together with previous findings in the field92728 were integrated into a general schema of tripartite interactions between bacteriophages, mammalian immunity and bacteria (Fig. 3) The schema summarizes main reciprocal dependencies, specifically limiting or inducing effects. The key assumptions for this schema were as follows (Fig. 3): first, adaptive immunity specific to phages and adaptive immunity specific to bacteria have no important cross-talk; second, phages are not able to boost innate immunity2728; third, boosted innate immunity acts against bacteria, but at the same time it also acts against the phage.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, 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.

No MeSH data available.


Related in: MedlinePlus