Phage induced anti-virale immune responses

Lysogenic phages, such as the P. aeruginosa filamentous phage Pf, are abundant at sites of bacterial infections (e.g. wounds). These filamentous phages are able to induce antiviral immune responses, through which they shut down the phagocytosis of its bacterial host. The uptake of Pf phage results in the activation of TLR3- and TIR domain-containing adapter inducing interferon-β (TRIF)–dependent type I interferon production. This leads to the inhibition of TNF-α productions and the suppression of phagocytosis. This indicates that Pf triggers maladaptive innate viral pattern-recognition responses that impair bacterial clearance, thereby implicating Pf phage in bacterial pathogenesis. Moreover, this immune activation is not instigated by the phage particle but through the production of phage RNA within the human cell. The precise mechanisms through which phage RNA is transcribed in mammalian cells is currently not known. These data are noteworthy because they suggest that a bacteriophage can “infect” mammalian cells. Further more these responses are in line with the previous in silico predictions regarding phage induced immune responses and their effect on the bacterial and human host.

Immunomodulation by bacteriophages

It is know that when phages are applied orally they can translocate to systemic tissues and end up in the bloodstream. This suggests that mammals have evolved mechanisms for the uptake and delivery of phages that may allow intestinal phages to elicit innate and adaptive immune responses. Several studies have shown that phages can trigger a host immune response. It has been shown that phages can inhibit the activation and proliferation of human T cells in vitro through unknown mechanisms. Phages are even able to induce an antibody response. So if phages are present everywhere and we are in constant contact with phages we can ask our self the question whether they interact with our immune system. More specifically, do they have anti-inflammatory properties? Otherwise how can they work systemically without inducing an immune response?