Mammalian Host-Versus-Phage immune response determines phage fate in vivo
Open accessAbstract
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.
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One significant challenge in clinical application is the complex interplay between administered phages and the human immune system.
“One significant challenge in clinical application is the complex interplay between administered phages and the human immune system [140–142]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [142]
Neutralizing antibodies can develop upon repeated phage exposure, potentially limiting long-term efficacy through enhanced clearance.
“Neutralizing antibodies can develop upon repeated phage exposure, potentially limiting long-term efficacy through enhanced clearance.”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [142]
Cytokine responses to phage administration, while potentially beneficial for tumor immunogenicity, could pose safety risks in immunosuppressed patients.
“Cytokine responses to phage administration, while potentially beneficial for tumor immunogenicity, could pose safety risks in immunosuppressed patients.”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [142]
The Discussion (page unavailable) proposes serum cytokine evaluations as future testing, but does not report cytokine responses to phage administration. The Results address LPS-induced inflammation and anti-phage antibodies; searches for tumor immunogenicity and safety risks in immunosuppressed patients found no passage addressing those claims. (LLM, conf=0.73)
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- Authors
- 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.
- Affiliations
- Ludwik Hirszfeld Institute of Immunology and Experimental Therapy (PL)
- Wrocław University of Science and Technology (PL)
- Corresponding author
- Dąbrowska, Krystyna
- ORCID
- Venue
- Scientific Reports
- Published
- 2015-10-06
- Volume
- 5
- Issue
- 1
- Pages
- 14802-14802
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4594097
- OpenAlex
- W1902380478
- Cited by
- 302
- References
- 2
- Citations by year
- 2026: 36 · 2025: 30 · 2024: 30 · 2023: 34 · 2022: 25 · 2021: 37 · 2020: 28 · 2019: 31 · 2018: 20 · 2017: 21 · 2016: 10
- FWCI
- 15.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Research Centre
- Krajowy Naukowy Osrodek Wiodacy (2014-2018, years 2014-2018)
- Topics
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- phage therapy, host immune response, complement system, innate immunity, adaptive immunity, mathematical modeling, phage-bacteria interactions, antibiotic resistance
- MeSH terms
- Animals, Immunity, Innate, Lipopolysaccharides, Macrophages, Male, Mammals, Mice, Inbred C57BL, Models, Theoretical, Phagocytosis, Pseudomonas Phages, Microscopy, Confocal, Systemic Inflammatory Response Syndrome, Host-Pathogen Interactions, Adaptive Immunity
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