Chapter 2 - Phage as a Modulator of Immune Responses: Practical Implications for Phage Therapy
Section snippets
Background
The vast majority of studies on phage biology have traditionally focused on the interactions of bacteriophages with bacterial cells. However, bacteriophages can also interact with some populations of mammalian cells, especially with immune cells. In fact, the first studies on the interactions between bacteriophages and immune cells were conducted by Felix d'Herelle shortly after the discovery of phages (d'Herelle, 1922). Since then, a considerable body of experimental data has accumulated to
Anti-phage humoral responses
Antiviral antibodies are one of the main components of antiviral immune responses. In the case of pathogenic viruses, these antibodies can exhibit four main activities: virus neutralization, antibody-dependent cellular cytotoxicity, antibody-dependent cell-mediated virus inhibition, and phagocytosis (Forthal and Moog, 2009).
Antibodies that were examined in the vast majority of studies on phage immunogenicity are neutralizing antibodies. Essentially, these are defined as antibodies that bind
Effects of phages on phagocytic cells
The activity of phagocytic cells constitutes one of the essential functions of antibacterial immune responses (Silva 2010). Investigating phage interactions with major populations of phagocytic cells may thus verify whether phages could eliminate bacteria in vivo not only by direct bactericidal activity, but also by activating phagocytic cells. Furthermore, interactions between endogenous phages (known to be present in very large numbers within normal microflora; Górski and Weber-Dąbrowska 2005
Phage Virion Inactivation by Immune Cells
Inchley (1969) showed that the majority of T4 phage particles are cleared rapidly from the circulation of mice by cells of the reticuloendothelial system of the liver and, to a lesser extent, of the spleen. However, experiments performed on nonimmune germ-free mice demonstrated that it is the spleen rather than the liver that clears most of the phage particles from the blood regardless of the route of phage administration (Geier et al., 1973). Interestingly, both studies consistently showed
Concluding Remarks
The aim of this chapter was to update and summarize existing knowledge on phage effects on the immune system. Evidently, such a report should be helpful in fully understanding the possible mechanisms of action of phage therapy and for appropriate planning of clinical trials, which would take into account different aspects of possible interactions of phages with the human organism. In this context, two questions are of paramount importance, namely: How does the immune system react to the
Acknowledgments
This work was supported by the European Regional Development Fund within the Operational Program Innovative Economy, 2007-2013, Priority axis 1. Research and Development of ModernTechnologies, Measure 1.3 Support for R&D projects for entrepreneurs carried out by scientific entities, Submeasure 1.3.1 Development projects as project No. POIG 01.03.01-02-003/08 entitled “Optimization of the production and characterization of bacteriophage preparations for therapeutic use”, by statutory funds from
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