Effect of bacteriophages on cytokine production by human peripheral blood mononuclear cells and their subpopulations
6 affiliations
- 1Bacteriophage Laboratory, Phage Therapy Department, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
- 2Department of Clinical Immunology, Medical University of Warsaw
- 3Laboratory of Cellular and Genetic Therapies, Center for Preclinical Research, Medical University of Warsaw
- 4Chair and Department of Medical Microbiology, Medical University of Warsaw
- 5Phage Therapy Unit, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
- 6Professor Emeritus, Department of Clinical Immunology, Medical University of Warsaw
Abstract
Introduction: Fulfilling a vision that extends beyond their role as antibiotic alternatives, bacteriophages are now recognized as active immunomodulators, a concept aligning with early hypotheses of their biological activity. In addition to their bactericidal action, these properties require detailed investigation. This study aims to characterize the immunomodulatory effects of bacteriophages on pro- and anti-inflammatory cytokine production by human immune cells isolated from healthy blood donors.
Methods: We assessed the secretion of a comprehensive panel of 11 cytokines (including IFN-γ, IL-6, TNF-α, and IL-10) by peripheral blood mononuclear cells and their isolated subpopulations (B and T lymphocytes, helper and cytotoxic T lymphocytes, natural killer cells, and monocytes). The cells were incubated for 24 hours with purified Escherichia coli phage T4 and therapeutic staphylococcal phage A5/80. Reference cells were incubated with lipopolysaccharide from E. coli B at a concentration corresponding to its activity in the applied phage preparations. For comparison, we also assessed cytokine responses to human adenovirus 5, used as a benchmark for a virus capable of infecting human cells.
Results: Cell-specific analysis revealed a distinct hierarchy in immune responsiveness: our data suggest that monocytes may act as the primary sensors driving cytokine signatures, while we did not confirm a discernible direct response in B, natural killer, and cytotoxic T cells. Importantly, the magnitude of these responses was markedly lower than the robust inflammatory cytokine secretion triggered by human adenovirus 5, providing context for the phage-induced effects relative to a viral infection of human cells and underscoring the limited inflammatory footprint of therapeutic phages.
Conclusion: These results improve our understanding of phage–human immune system interactions, which is important for appreciating their broader impact on human homeostasis and for assessing the safety of phage therapy.
Related
- Single-cell RNA sequencing delineates compositional and transcriptional changes of porcine peripheral blood mononuclear cell populations following Salmonella I 4,[5],12:i:- inoculation
- Novel human long noncoding RNA responses to Candida auris and its cell-wall components in peripheral blood mononuclear cells
- Peripheral blood mononuclear cells as a novel source for mitochondrial transplantation therapy in peripheral nerve injury repair
- Single-cell transcriptome sequencing analysis of peripheral blood mononuclear cells reveals immune signatures in patients with polymyalgia rheumatica
- Personalized Nutrition for Immune Optimization: A Nutrigenetic Approach to the Peripheral Blood Mononuclear Cell Response
BibTeX
@article{kasprzak2026effect,
title = {{Effect of bacteriophages on cytokine production by human peripheral blood mononuclear cells and their subpopulations}},
author = {Hubert Kasprzak and Monika Kniotek and Katarzyna Zielniok and Maciej Przybylski and Andrzej Górski and Ryszard Międzybrodzki},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1916240},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1916240/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effect of bacteriophages on cytokine production by human peripheral blood mononuclear cells and their subpopulations
AU - Hubert Kasprzak
AU - Monika Kniotek
AU - Katarzyna Zielniok
AU - Maciej Przybylski
AU - Andrzej Górski
AU - Ryszard Międzybrodzki
PY - 2026
DA - 2026/10/13
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1916240
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1916240/full
AB - Introduction: Fulfilling a vision that extends beyond their role as antibiotic alternatives, bacteriophages are now recognized as active immunomodulators, a concept aligning with early hypotheses of their biological activity. In addition to their bactericidal action, these properties require detailed investigation. This study aims to characterize the immunomodulatory effects of bacteriophages on pro- and anti-inflammatory cytokine production by human immune cells isolated from healthy blood donors. Methods: We assessed the secretion of a comprehensive panel of 11 cytokines (including IFN-γ, IL-6, TNF-α, and IL-10) by peripheral blood mononuclear cells and their isolated subpopulations (B and T lymphocytes, helper and cytotoxic T lymphocytes, natural killer cells, and monocytes). The cells were incubated for 24 hours with purified Escherichia coli phage T4 and therapeutic staphylococcal phage A5/80. Reference cells were incubated with lipopolysaccharide from E. coli B at a concentration corresponding to its activity in the applied phage preparations. For comparison, we also assessed cytokine responses to human adenovirus 5, used as a benchmark for a virus capable of infecting human cells. Results: Cell-specific analysis revealed a distinct hierarchy in immune responsiveness: our data suggest that monocytes may act as the primary sensors driving cytokine signatures, while we did not confirm a discernible direct response in B, natural killer, and cytotoxic T cells. Importantly, the magnitude of these responses was markedly lower than the robust inflammatory cytokine secretion triggered by human adenovirus 5, providing context for the phage-induced effects relative to a viral infection of human cells and underscoring the limited inflammatory footprint of therapeutic phages. Conclusion: These results improve our understanding of phage–human immune system interactions, which is important for appreciating their broader impact on human homeostasis and for assessing the safety of phage therapy.
SN - 1664-3224
ER -