Table 1: Immunomodulatory effects of bacteriophage exposure.

Phage interactionsImmunomodulatory effectsReference

Phage-phagocyte interactions in antitumor therapiesPhages expressing Fab fragment specific for tumor accumulated in the tumor tissue and induced humoral and cellular immune responses, leading to solid tumor regression in mice.[22]
T4 phages interacting with B3 integrins modulated the function of human T cells and platelets. Bone marrow dendritic cells did not confer similar results, but a significant delay in tumor growth was observed.[26, 27]

Antiphage immune responseAs foreign exogenous antigens, phages induce strong antiphage humoral responses resulting in rapid and efficient neutralization and clearance upon subsequent exposure. Phages circulating in the blood were inactivated by macrophages of the RES in synergy with antiphage antibodies—an outcome that would quickly diminish the efficacy of phage therapy upon subsequent exposures. Repeated use of a phage as a therapeutic, in addition to the interactions with the innate immune system, would result in the stimulation of memory cells, clone amplification, and subsequent antibody production.
Phage mutagenesis followed by repeated administration of phage therapy and selection for long-circulating phage is an elegant method that permitted investigators to select and isolate mutant phage that persevere from the blood of a mouse.
[22, 28, 29]

Bacteriophages and Reactive Oxygen Species ProductionPhage-mediated inhibition of ROS production by phagocytes is an important phenomenon contributing to the beneficial effects of phage therapy in patients with sepsis, a clinical setting where excessive production of ROS appears to play an important role, and agents interfering with ROS have been advocated for treatment.[22]