Table 2.

Examples of the influence of bacteriophages on immune responses in animals.

Kind of Phage	Form of Application	Animal Model	Influence on Immune Parameters	References
Pseudomonas spp. bacteriophage (PA1Ø)	100 µL of PA1Ø (5 × 104 PFU; 5 × 107 PFU (10 MOI) or 5 × 108 PFU (100 MOI) in a single i.p. dose	4–5-week-old male ICR mice weighing 24–26 g	Increase in phagocytosis (killing effect of PA1Ø + PMN up to 6 h after application)	[65]
Pseudomonas aeruginosa phage PAK_P1	Intranasally at a curative dose of 1.0 × 108 PFU or 1.0 × 109 PFU	Wild-type BALB/c (C), wild-type C57Bl6/J (B6)	Increase in neutrophil activity, NK cells; reduced production of IFNγ and TNFα	[75]
Cronobacter sakazakii ES2 phage	Phage suspension 106 PFU·mL−1 in vitro	6–8-week-old C57BL/6 mice	Increase in expression of maturation markers CD86, CD40, and MHC II; stimulation of induction of NF-κBp65-mediated-IL-12p40; stimulation of IL-12 expression; suppression of IL-6, TNF-α, IL-1β, and IFN-γ	[62]
E. coli T4 phage	Intraperitoneal injection at 20 µg/mouse	Female C57Bl6/J (6–8-week-old) mice	No effect on production of cytokines IL-1α, IL-6, IL-12, and TNF-α; minor changes in expression of MHC II, CD40, CD86, and CD80	[76]
E.coli T4 bacteriophages	T4 phages 5 × 108 PFU/mL	8–12-week-old female C57BL/6 mice	Inhibition of specific antibody response; reduction in bacteria-induced ROS production by phagocytic cells; antitumour response; activation of T cells for IFN-γ production	[77]
E. coli P1 and P2 phages	106 PFU/mL in vitro	Mice	Stimulation of TNFα; stimulation of macrophage activity in vitro	[78]
Wild-type E. coli T7 phage	109 PFU/mL injected in vitro into tail vein of mice	Adult female C57BL/6J, SCID (C57BL/6J-Prkdcscid), B-cell-deficient (C57BL/10-Igh-6tm1Cgn) and T-cell deficient (C57BL/6J-Hfh11nu) mice	Spontaneous antibodies, mainly IgM, observed in sera; slight effect on NK activation; anti-inflammatory effect—ROS suppression	[79]
Wild-type E.coli φ26, φ27, φ29	107–108 PFU/mL for 5 days per rectum as suppositories	25 newborn HF calves aged 1 d to 2 weeks	Significant increase in IgG and IgA production stimulation of nonspecific immune response—IFNγ, lysozyme; activation of acute phase response SAA and HP	[41]
Wild-type E.coli phage and bacteriophage genomes NC-A: MK310182; NC-B: MK310183; NC-G: MK310184	3 × 107 PFU/mL of phage mixture with drinking water	8-week-old germ-free Swiss Webster mice	Whole bacteriophages and phage DNA stimulated IFN-γ via nucleotide-sensing receptor TLR9	[80]
S. aureus vB_SauM_JS25 phage	MAC-T cells pre-treated with vB_SauM_JS25 phage 108 PFU/well for 3 h	In vitro MAC-T bovine mammary epithelial cells	Reduction in TNF-α, IL-1β, IL-6, IL-8, and IL-10	[54]
Staphylococcus spp. bacteriophage A3R or 676Z	3 doses of 1010 PFU/mouse in drinking water and peritoneally	C57BL/6J normal male mice	Induction of specific antibodies in blood (IgM, IgG, IgA)	[81]
Klebsiella pneumoniae MTCC109 bacteriophage PA43	Intranasal application of 109 PFU BPA43 phage after 2 h of bacterial infection	BALB/c mice, 6–8 weeks old, weight 20–25 g	Suppression of local inflammatory reaction in lungs; suppression of migration of lymphocytes and macrophages	[82]