Figure 5.

Effects of innate and adaptive immunity on the success or failure of phage antibacterial treatment, numerical simulations. Innate immune response. (A) No relation between innate immunity and phage viability. The survival of the phage is independent of the presence of an innate immune response. (B) Phage susceptibility to the innate immune response. The innate immunity has a negative effect on the phage survival and leads to its removal. Subsequently the bacteria are no longer infected by the phage, and a rise in bacteria is observed. (C) Phage susceptibility to the innate immune response, considering the anti-inflammatory property of the phage. The anti-inflammatory characteristic of the phage leads to a decline in innate immune particles. This has as effect that the bacterial count diminishes, and the phage survives, similar to A. (D) Phage susceptibility to innate immune response accommodated and counteracted by an increased phage dose. The higher phage dose leads to the removal of the pathogen and the survival of the phage. (E) Phage susceptibility to innate immune response accommodated and counteracted by an increased phage dose, considering the anti-inflammatory property of the phage. The effect is the same as in D, but the innate immune response is diminished. Innate and adaptive immune response. (F) Phage susceptibility to the innate immune response and presence of pre-immunization towards the phage. Presence of pre-existing anti-phage antibodies lead to a rapid drop in phage concentration, hence the phage has no effect on the survival of the bacteria. Once an adaptive immune response towards the bacteria is present, bacterial count decreases. (G) Phage susceptibility to the innate immune response and no pre-immunization to the phage exists, considering the anti-inflammatory property of the phage. The anti-inflammatory response of the phage has no direct influence on the phage survival in the presence of an adaptive immune response towards the phage. Overall the response is similar to F. (H) Phage susceptibility to the innate immune response and no pre-immunization to the phage exists. The absence of a specific adaptive immune response towards the phage leads to a decrease in the bacterial population. The combined effect of innate and adaptive immunity towards the phage leads to a drop-in phage particle concentration. (I) Phage susceptibility to the innate immune response and no pre-immunization to the phage exists, considering the anti-inflammatory property of the phage. Once the phage reaches a critical concentration (Pc, the concentration of phages needed to induce an anti-inflammatory response), the innate immune response decreases, and the phage concentration grows until all bacteria are removed. Once an adaptive immune response is present against the phage, the phage concentration diminishes until completely removed. Variables and parameters used in these models are described in Tables S1 and S2.