Phage Interaction with the Mammalian Immune System

Belleghem, Jonas Van; Dąbrowska, Krystyna; Vaneechoutte, Mario; Barr, Jeremy J.

doi:10.1007/978-3-030-26736-0_4

Cited by 9 publications

(8 citation statements)

References 249 publications

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“…These studies, however, have failed to find much of a correlation to either presence or absence of phage therapy efficacy (Łusiak-Szelachowska et al, 2014;. For recent reviews of phage-immune system interactions, see (Dąbrowska et al, 2018;Dąbrowska, 2019;Dąbrowska and Abedon, 2019;Van Belleghem et al, 2019;Żaczek et al, 2019).…”

Section: (7)mentioning

confidence: 99%

Phage Therapy: The Pharmacology of Antibacterial Viruses

Danis-Wlodarczyk¹,

Dąbrowska²,

Abedon³

2021

Current Issues in Molecular Biology

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Pharmacology can be differentiated into two key aspects, pharmacodynamics and pharmacokinetics. Pharmacodynamics describes a drug's impact on the body while pharmacokinetics describes the body's impact on a drug. Another way of understanding these terms is that pharmacodynamics is a description of both the positive and negative consequences of drugs attaining certain concentrations in the body while pharmacokinetics is concerned with our ability to reach and then sustain those concentrations. Unlike the drugs for which these concepts were developed, including antibiotics, the bacteriophages (or 'phages') that we consider here are not chemotherapeutics but instead are the viruses of bacteria. Here we review the pharmacology of these viruses, particularly as they can be employed to combat bacterial infections (phage therapy). Overall, an improved pharmacological understanding of phage therapy should allow for more informed development of phages as antibacterial 'drugs', allow for more rational post hoc debugging of phage therapy experiments, and encourage improved design of phage therapy protocols. Contrasting with antibiotics, however, phages as viruses impact individual bacterial cells as single virions rather than as swarms of molecules, and while they are killing bacteria, caister.com/cimb 81 Curr. Issues Mol. Biol. Vol. 40bacteriophages also can amplify phage numbers, in situ. Explorations of phage therapy pharmacology consequently can often be informed as well by basic principles of the ecological interactions between phages and bacteria as by study of the pharmacology of drugs. Bacteriophages in phage therapy thus can display somewhat unique as well as more traditional pharmacological aspects.

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Section: (7)mentioning

confidence: 99%

Phage Therapy: The Pharmacology of Antibacterial Viruses

Danis-Wlodarczyk¹,

Dąbrowska²,

Abedon³

2021

Current Issues in Molecular Biology

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Section: (7)mentioning

confidence: 99%

Phage Therapy: The Pharmacology of Antibacterial Viruses

Danis-Wlodarczyk¹,

Dąbrowska²,

Abedon³

2020

Bacterial Viruses: Exploitation for Biocontrol and Therapeutics

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Pharmacology can be differentiated into two key aspects, pharmacodynamics and pharmacokinetics. Pharmacodynamics describes a drug's impact on the body while pharmacokinetics describes the body's impact on a drug. Another way of understanding these terms is that pharmacodynamics is a description of both the positive and negative consequences of drugs attaining certain concentrations in the body while pharmacokinetics is concerned with our ability to reach and then sustain those concentrations. Unlike the drugs for which these concepts were developed, including antibiotics, the bacteriophages (or 'phages') that we consider here are not chemotherapeutics but instead are the viruses of bacteria. Here we review the pharmacology of these viruses, particularly as they can be employed to combat bacterial infections (phage therapy). Overall, an improved pharmacological understanding of phage therapy should allow for more informed development of phages as antibacterial 'drugs', allow for more rational post hoc debugging of phage therapy experiments, and encourage improved design of phage therapy protocols. Contrasting with antibiotics, however, phages as viruses impact individual bacterial cells as single virions rather than as swarms of molecules, and while they are killing bacteria, 49 bacteriophages also can amplify phage numbers, in situ. Explorations of phage therapy pharmacology consequently can often be informed as well by basic principles of the ecological interactions between phages and bacteria as by study of the pharmacology of drugs. Bacteriophages in phage therapy thus can display somewhat unique as well as more traditional pharmacological aspects. Abd El-Aziz, A.M., Elgaml, A., and Ali, Y.M. (2019). Bacteriophage therapy increases complement-mediated lysis of bacteria and enhances bacterial clearance after acute lung infection with multidrug-resistant Pseudomonas aeruginosa.

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“…The few studies that have investigated the cellular and innate immune response to phages have hinted at two opposing responses. On the one hand, certain phages are known to induce anti-inflammatory effects (24,25). This has led to suggestions that phages could be used in transplantation patients to reduce risks of organ rejection (25,26) and may play an immunomodulatory role in the gut microbiome (27,28).…”

Section: Introductionmentioning

confidence: 99%

“…Phages internalized via this pathway steadily accumulate within intracellular macropinosomes (14). The downstream processing of the macropinosome can follow various pathways, including fusion with other endocytic vesicles, fusion with lysosomes leading to acidification and the inactivation of internalized components, recycling and transport to plasma membranes, and constitutive exocytosis (24).…”

Section: Introductionmentioning

confidence: 99%

Mammalian cells internalize bacteriophages and utilize them as a food source to enhance cellular growth and survival

Bichet

Adderley

Avellaneda-Franco

et al. 2023

Preprint

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There is a growing appreciation that the direct interaction between bacteriophages and the mammalian host can facilitate diverse and unexplored symbioses. Yet the impact these bacteriophages may have on mammalian cellular and immunological processes is poorly understood. Here we applied highly purified phage T4, free from bacterial by-products and endotoxins to mammalian cells and analyzed the cellular responses using luciferase reporter and antibody microarray assays. Phage preparations were applied in vitro to either A549 lung epithelial cells, MDCK-I kidney cells, or primary mouse bone marrow derived macrophages with the phage-free supernatant serving as a comparative control. Highly purified T4 phages were rapidly internalized by mammalian cells and accumulated within macropinosomes but did not activate the inflammatory DNA response TLR9 or cGAS-STING pathways. Following eight hours of incubation with T4 phage, whole cell lysates were analyzed via antibody microarray that detected expression and phosphorylation levels of human signaling proteins. T4 phage internalization led to the activation of AKT-dependent pathways, resulting in an increase in cell metabolism, survival, and actin reorganization, the last being critical for macropinocytosis and potentially regulating a positive feedback loop to drive further phage internalization. T4 phages additionally down-regulated CDK1 and its downstream effectors, leading to an inhibition of cell cycle progression and an increase in cellular growth through a prolonged G1 phase. These interactions demonstrate that highly purified T4 phages do not activate DNA-mediated inflammatory pathways but do trigger protein phosphorylation cascades that promote cellular growth and survival. We conclude that mammalian cells are internalizing bacteriophages as a food source to promote cellular growth and metabolism.

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Phage Interaction with the Mammalian Immune System

Cited by 9 publications

References 249 publications

Phage Therapy: The Pharmacology of Antibacterial Viruses

Phage Therapy: The Pharmacology of Antibacterial Viruses

Phage Therapy: The Pharmacology of Antibacterial Viruses

Mammalian cells internalize bacteriophages and utilize them as a food source to enhance cellular growth and survival

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