The field of bacteriophage research is rapidly evolving, offering new perspectives on the complex interplay between phages, bacteria, and host immune systems. Although traditionally viewed as specialized viruses that infect and eliminate bacteria, recent advances reveal that bacteriophages exert direct and indirect influences on the mammalian immune system. Their ability to engage with immune cells such as macrophages, dendritic cells, and lymphocytes positions them as significant contributors to immune homeostasis and inflammation regulation. Notably, both experimental and clinical studies have demonstrated that phages can modulate immune signaling, alter cytokine environments, and potentially reshape the outcomes of infectious and inflammatory diseases. Despite these developments, uncertainties persist regarding the precise molecular and cellular mechanisms through which phages communicate with and influence immune pathways, the diversity of immunological outcomes elicited, and the factors that determine beneficial versus adverse responses. A deeper understanding of these processes is critical in light of the renewed interest in phage therapy for tackling antibiotic-resistant infections and as potential immunomodulatory agents.

This Research Topic aims to systematically elucidate the multifaceted interactions between bacteriophages and the immune system across both basic and applied contexts. By bringing together expertise from microbiology, immunology, and translational medicine, the goal is to define how phages are detected and processed by immune cells, clarify the spectrum of immune activation and suppression they can induce, and critically assess their safety and efficacy in therapeutic settings. Central questions include how bacteriophages are recognized by innate and adaptive immune components, what molecular signatures determine immunogenicity or tolerance, and how phage-derived interventions might be tailored to achieve desired immune outcomes. Articles addressing the influence of formulation, administration routes, and host microbiota on immunological interfaces are also sought, aiming to inform better strategies for safe and effective phage application in medicine.

This Research Topic will cover experimental, computational, and theoretical studies examining the intricate relationship between bacteriophages and the immune system. The scope is limited to mechanistic, immunological, and translational aspects of phage–host immunity in both preclinical and clinical models, without focusing on broader ecological or evolutionary questions. To gather further insights into phage–immunity dynamics and their therapeutic applications, we welcome articles addressing, but not limited to, the following themes:

-Molecular and cellular mechanisms of phage recognition by immune cells
-Phage-induced modulation of innate and adaptive immune responses
-Immunological safety, tolerance, and possible immunopathology associated with phage therapy
-Triangular interactions among phages, host microbiota, and the immune system
-Preclinical and clinical studies exploring the immune consequences of phage administration

The topic editors declare no conflict of interest

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Immunological interfaces of bacteriophages: From basic mechanisms to therapeutic potential