T4 phage and its head surface proteins do not stimulate inflammatory mediator production

• Published in: PloS one Vol. 8; no. 8; p. e71036
• Main Authors: Miernikiewicz, Paulina, Dąbrowska, Krystyna, Piotrowicz, Agnieszka, Owczarek, Barbara, Wojas-Turek, Justyna, Kicielińska, Jagoda, Rossowska, Joanna, Pajtasz-Piasecka, Elżbieta, Hodyra, Katarzyna, Macegoniuk, Katarzyna, Rzewucka, Kamila, Kopciuch, Agnieszka, Majka, Tomasz, Letarov, Andrey, Kulikov, Eugene, Maciejewski, Henryk, Górski, Andrzej
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.08.2013; Public Library of Science (PLoS)
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - immunology; Avian flu; Bacteria; Bacterial infections; Bacteriophage T4 - chemistry; Biology; Blood; Blood cells; Bone marrow; Capsid Proteins - pharmacology; CD40 antigen; CD80 antigen; CD86 antigen; Chemiluminescence; Chemokines; Cytokines; Cytokines - genetics; Cytokines - immunology; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Female; Gene Expression; Granulocyte-macrophage colony-stimulating factor; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; HIV; Human immunodeficiency virus; Humans; Immune system; Immunity; Immunology; Inflammation; Interferon; Interleukin 10; Interleukin 12; Interleukin 2; Interleukin 6; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Major histocompatibility complex; Mammals; Mice; Mice, Inbred C57BL; Monocyte chemoattractant protein 1; Oxygen; Phages; Proteins; RANTES; Reactive oxygen species; Reactive Oxygen Species - metabolism; Staphylococcus infections; Stimulators; Studies; Therapy; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Veterinary medicine; Viral proteins; Viruses; γ-Interferon; Poland; Russia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0071036

Viruses are potent activators of the signal pathways leading to increased cytokine or ROS production. The effects exerted on the immune system are usually mediated by viral proteins. Complementary to the progress in phage therapy practice, advancement of knowledge about the influence of bacteriophages on mammalian immunity is necessary. Particularly, the potential ability of phage proteins to act like other viral stimulators of the immune system may have strong practical implications for the safety and efficacy of bacteriophage therapy. Here we present studies on the effect of T4 phage and its head proteins on production of inflammatory mediators and inflammation-related factors: IL-1α, IL-1β, IL-2, IL-6, IL-10, IL-12 p40/p70, IFN-γ, TNF-α, MCP-1, MIG, RANTES, GCSF, GM-CSF and reactive oxygen species (ROS). Plasma cytokine profiles in an in vivo mouse model and in human blood cells treated with gp23*, gp24*, Hoc and Soc were evaluated by cytokine antibody arrays. Cytokine production and expression of CD40, CD80, CD86 and MHC class II molecules were also investigated in mouse bone marrow-derived dendritic cells treated with whole T4 phage particle or the same capsid proteins. The influence of T4 and gp23*, gp24*, Hoc and Soc on reactive oxygen species generation was examined in blood cells using luminol-dependent chemiluminescence assay. In all performed assays, the T4 bacteriophage and its capsid proteins gp23*, gp24*, Hoc and Soc did not affect production of inflammatory-related cytokines or ROS. These observations are of importance for any medical or veterinary application of bacteriophages.