The Effects of T4 and A3/R Bacteriophages on Differentiation of Human Myeloid Dendritic Cells

Abstract

Bacteriophages (phages) are viruses of bacteria. Here we evaluated the effects of T4 and A3/R bacteriophages, as well as phage-generated bacterial lysates, on differentiation of human myeloid dendritic cells (DCs) from monocytes. Neither of the phages significantly reduced the expression of markers associated with differentiation of DCs and their role in the activation of T cells (CD40, CD80, CD83, CD86, CD1c, CD11c, MHC II, PD-L1, PD-L2, TLR2, TLR4, and CCR7) and phagocytosis receptors (CD64 and DEC-205). By contrast, bacterial lysate of T4 phage significantly decreased the percentages of DEC-205- and CD1c-positive cells. The percentage of DEC-205-positive cells was also significantly reduced in DCs differentiated in the presence of lysate of A3/R phage. Thus while bacteriophages do not substantially affect differentiation of DCs, some products of phage-induced lysis of bacterial cells may influence the differentiation and potentially also some functions of DCs. Our results have important implications for phage therapy of bacterial infections because during infections monocytes recruited to the site of inflammation are an important source of inflammatory DCs.

Interactions of Bacteriophages with Animal and Human Organisms—Safety Issues in the Light of Phage Therapy

“…This is primarily due to their ability to move across the endothelial cell barriers. In the study by Bochkareva et al [22], rectally administered phages against Pseudomonas aeruginosa, Salmonella enteritidis, and Escherichia coli were detected in blood samples at all investigation time points (30,45,60,75 min and 3, 6, 9 h). Two detection methods, microbiological agar-layer technique and PCR, confirmed the presence of phage DNA in blood samples collected from the rabbits, with the probability increasing between 3 and 6 h after suppository administration, depending on the type of phage.…”

Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics

“…The effect of the T4 and A3/R purified phages and their lysates on differentiation of human myeloid dendritic cells has been investigated to some degree [ 49 ]. Neither of the tested phages influenced the expression of the markers responsible for maturation of DC and activation of T cells, such as CD40, CD80, CD83, CD86, CD1c, CD11c, MHC class II, PD-L1, PD-L2, TLR2, TLR4, and CCR7.…”

“…Whereas, according to Górski et al (2012) the T4 phage did not affect the percentage of TLR2 and TLR4 ++ cells, as was observed in in vitro experiments in both monocytes stimulated and those not stimulated by LPS [ 20 ]. Also in myeloid DC, which were differentiated with the addition of the A3/R lysate, the presence of DEC205 was reduced [ 49 ]. It was observed that the level of IL-12 produced by the myeloid DC in the presence of the T4 and A3/R phages was undetectable, which may confirm that phages do not have an influence on the activation of mDC.…”

Effects of Staphylococcus aureus Bacteriophage K on Expression of Cytokines and Activation Markers by Human Dendritic Cells In Vitro

“…After oral administration of three E. coli O157:H7 phages to mice, all cytokine levels remained within normal ranges [ 14 ]. Purified phages T4 and A3/R had no effect on differentiation of human dendritic cells while crude phage lysates significantly reduced the expression of markers associated with differentiation [ 15 ]. Interestingly, mouse dendritic cells exposed to phage T4 had enhanced anti-tumor effect [ 16 ].…”