Two teams from the Institut Pasteur, in partnership with researchers from Inserm and the Georgia Institute of Technology in the U.S., have demonstrated that in order to ensure the efficacy of phage therapy applied in vivo during bacterial infection, bacteriophages rely on the host's immune response. This synergy is largely based on the crucial action of neutrophil immune cells. The discovery provides insights into the therapeutic action of phages in the treatment of certain bacterial infections.

The findings were published in the journal Cell Host & Microbe on July 12, 2017.

Until now, there has been insufficient scientific data to understand how phage therapy works in vivo. While most in vitro studies have proven that phages specifically target and kill bacteria, none of these studies took account of the importance of the host's response to this activity.

Two Institut Pasteur teams (Laurent Debarbieux's Bacteriophage–Bacteria Interactions in Animals Group and the Innate Immunity Unit led by James di Santo (Inserm U1223)) in partnership with Joshua Weitz's team at the Georgia Institute of Technology (Atlanta, U.S.), recently showed the importance of patients' immune status in terms of the chances of phage therapy success. This finding is the result of an original dual approach combining an animal model and mathematical modeling.

In order to evaluate the efficacy of treatment with a single phage species, the researchers focused on the bacterium Pseudomonas aeruginosa, which is involved in respiratory infections such as pneumonia. This bacterium, which is resistant to carbapenems, or 'antibiotics of last resort', was ranked by WHO as one of the four biggest global threats in terms of antibiotic resistance.

The researchers demonstrated that phage therapy is effective in animals with a healthy immune system (known as 'immunocompetent'). The innate immune system can be triggered quickly and phages initially act in tandem with it to fight off infection. Then, after 24 to 48 hours, some bacteria naturally develop resistance to the phages which consequently cease to function. The innate immune system then takes over to destroy the bacteria. Of all the immune cells involved, neutrophils play a predominant role.

In parallel, in silico simulations have shown that the innate response needs to destroy 20–50% of the bacteria in order for phage therapy to be effective, regardless of whether phage resistance is observed. Thus, in the model studied, the researchers proved that there are no circumstances under which phages are capable of eradicating a P. aeruginosa infection alone.

These findings are particularly significant since they suggest that patients' immune status should be considered when undertaking phage therapy. Laurent Debarbieux explains: "In terms of clinical consequences, one could reconsider the selection of patients likely to benefit from phage therapy. It may not be appropriate or recommended for people with severe immunodeficiency".