Phage as a Modulator of Immune Responses

Górski, Andrzej; Międzybrodzki, Ryszard; Borysowski, Jan; Dąbrowska, Krystyna; Wierzbicki, Piotr; Ohams, Monika; Korczak-Kowalska, G; Olszowska-Zaremba, Natasza; Łusiak-Szelachowska, Marzanna; Kłak, Marlena; Jończyk, Ewa; Kaniuga, Ewelina; Gołaś, Aneta; Purchla, Sylwia; Weber‐Dąbrowska, Beata; Letkiewicz, Sławomir; Fortuna, Wojciech; Szufnarowski, Krzysztof; Pawełczyk, Z; Rogóż, Paweł; Kłosowska, D

doi:10.1016/b978-0-12-394438-2.00002-5

Cited by 219 publications

(144 citation statements)

References 60 publications

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“…The recent review discusses in detail those immunomodulating activities of phages 11. In brief, phages can diminish T cell activation, alloantigen‐induced immunoglobulin production in vitro and extend the skin allograft survival in naive and sensitized mice 13, 14. In addition, phages may reduce autoimmune reaction when a mouse model of autoimmunity was used (collagen‐induced arthritis) 12.…”

Section: Phages As Immunomodulatorsmentioning

confidence: 99%

“…Phages do not impair granulocyte and monocyte ability to kill bacteria; conversely, this activity may be normalized in patients on phage therapy who had abnormally low values prior to the therapy (a finding with prognostic significance for the outcome of the therapy) 14. Capturing of lipopolysaccharide (LPS) does not appear to be responsible for this effect, as it is observed using phages against both Gram – and Gram + bacteria.…”

Section: Phages As Immunomodulatorsmentioning

confidence: 99%

“…In the face of increasing drama of anti‐microbial resistance, phages offer a broad medical promise as a weapon against antibiotics‐resistant bacteria 10. However, phages should no longer be considered as mere bacterial viruses but also as potential modulators of immunity 11, 12, 13, 14, 15, 16, a finding which may have an important application in therapy including autoimmune diseases 12.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic potential of phages in autoimmune liver diseases

Górski

Jończyk‐Matysiak

Łusiak-Szelachowska

et al. 2018

Clinical and Experimental Immunology

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SummaryAutoimmune liver disease (ALD) poses a difficult medical challenge, as there is a significant number of patients in whom current therapy offers questionable or no benefit, yet its side effects may be serious, including the development of malignancy. Bacterial viruses (phages) have been recognized increasingly as immunomodulators contributing to immune homeostasis and curbing inflammation. Accumulating data suggest that phages may be useful in immunotherapy of ALD. Phages have been shown to down‐regulate the expression and/or production and activity of factors associated with hepatic injury [reactive oxygen species, Toll‐like receptor (TLR)‐4 activation, nuclear factor kappa B (NF‐κB) activation, proinflammatory and procoagulant activities of platelets] and up‐regulate the expression and/or production of factors demonstrated as playing a protective role [interleukin (IL)‐10, IL‐1 receptor antagonist].

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Section: Phages As Immunomodulatorsmentioning

confidence: 99%

Section: Phages As Immunomodulatorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic potential of phages in autoimmune liver diseases

Górski

Jończyk‐Matysiak

Łusiak-Szelachowska

et al. 2018

Clinical and Experimental Immunology

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“…One of the concerns associated with the use of phages in the treatment of bacterial infections is the capacity of the human immune system to neutralize them due to their immunogenicity (39). Hodyra-Stefaniak et al demonstrated that in murine models of the systemic inflammatory response, there is a decrease in the availability of active phages in circulation and in numerous tissues due to the action of phagocytes, antibodies, and the serum complement system (135).…”

Section: Engineered Phages With Reduced Impacts On Mammalian Systemsmentioning

confidence: 99%

“…Obtaining regulatory approval for the therapeutic applications of such cocktails can be challenging because of the significant diversity of phages in terms of structure, life cycle, and genome organization (22,38). Like certain antibiotics, phages can cause rapid and massive bacterial lysis and the subsequent release of cell wall components (e.g., lipopolysaccharides [LPS]), which can induce adverse immune responses in the human host (39,40). Bacteria frequently live in biofilm communities surrounded by extracellular polymeric substances (EPS), which can act as a barrier to phage penetration (41).…”

mentioning

confidence: 99%

Genetically Engineered Phages: a Review of Advances over the Last Decade

Pires

Cleto

Sillankorva

et al. 2016

Microbiol Mol Biol Rev

335

275

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SUMMARYSoon after their discovery in the early 20th century, bacteriophages were recognized to have great potential as antimicrobial agents, a potential that has yet to be fully realized. The nascent field of phage therapy was adversely affected by inadequately controlled trials and the discovery of antibiotics. Although the study of phages as anti-infective agents slowed, phages played an important role in the development of molecular biology. In recent years, the increase in multidrug-resistant bacteria has renewed interest in the use of phages as antimicrobial agents. With the wide array of possibilities offered by genetic engineering, these bacterial viruses are being modified to precisely control and detect bacteria and to serve as new sources of antibacterials. In applications that go beyond their antimicrobial activity, phages are also being developed as vehicles for drug delivery and vaccines, as well as for the assembly of new materials. This review highlights advances in techniques used to engineer phages for all of these purposes and discusses existing challenges and opportunities for future work.

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Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

Dąbrowska

2019

Medicinal Research Reviews

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245

212

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Bacteriophages are not forgotten viruses anymore: scientists and practitioners seek to understand phage pharmacokinetics in animals and humans, investigating bacteriophages as therapeutics, nanocarriers or microbiome components. This review provides a comprehensive overview of factors that determine phage circulation, penetration, and clearance, and that in consequence determine phage applicability for medicine. It makes use of experimental data collected by the phage community so far (PubMed 1924‐2016, including non‐English reports), combining elements of critical and systematic review. This study covers phage ability to enter a system by various routes of administration, how (and if) the phage may access various tissues and organs, and finally what mechanisms determine the courses of phage clearance. The systematic review method was applied to analyze (i) phage survival in the gut (gut transit) and (ii) phage ability to enter the mammalian system by many administration routes. Aspects that have not yet been covered by a sufficient number of reports for mathematical analysis, as well as mechanisms underlying trends, are discussed in the form of a critical review. In spite of the extraordinary diversity of bacteriophages and possible phage applications, the analysis revealed that phage morphology, phage specificity, phage dose, presence of sensitive bacteria or the characteristics of treated individuals (age, taxonomy) may affect phage bioavailability in animals and humans. However, once phages successfully enter the body, they reach most organs, including the central nervous system. Bacteriophages are cleared mainly by the immune system: innate immunity removes phages even when no specific response to bacteriophages has yet developed.

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Phage as a Modulator of Immune Responses

Cited by 219 publications

References 60 publications

Therapeutic potential of phages in autoimmune liver diseases

Therapeutic potential of phages in autoimmune liver diseases

Genetically Engineered Phages: a Review of Advances over the Last Decade

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

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