Bacteriophages: Uncharacterized and Dynamic Regulators of the Immune System

Figure 2

Crosstalk between phages and the immune system. (a) Indirect influences on immune responses. Phage infection may lead to the release of PAMPs, which can translocate the gut epithelium and induce proinflammatory responses. In the case of imbalanced phage communities, infection of certain bacterial species may lead to an altered microbiota, overgrowth of pathogens, and chronic inflammation. Prophage-encoded genes can aid pathogens in their abilities to damage and invade the epithelium and evade the immune system by directly inhibiting phagocytic cells. Sequestration of iron by phage tail domains could prevent pathogen overgrowth in the intestines. Binding of LPS by phage head proteins may dampen LPS-induced inflammation. (b) Direct stimulation of immune responses. Phages may cross the intestinal epithelium in 3 ways: nonspecific transcytosis, specific recognition of eukaryotic cells via structures that resemble bacterial receptors, and passage through damaged epithelial cells with defects in permeability. Once in the lamina propria, phages can interact with the intestinal immune system to generate pro- or anti-inflammatory responses and generate specific antiphage-neutralizing antibodies. The image was created using BioRender.

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