Max Gutierrez, head of the Host-Pathogen Interactions in Tuberculosis Laboratory at the Crick, said: “I first studied the role of autophagy in infection during my PhD, so it’s incredible to see renewed interest in this field. Using the latest technologies, we’ve been able to show a key role for this pathway in controlling infection.
“As immunotherapies have harnessed the immune system to fight cancer, boosting this immune defence with a host-directed therapy, could be a valuable new tool in the fight against infections, particularly those becoming resistant to antibiotics.”
The team also validated their results using macrophages isolated from blood samples, confirming the importance of autophagy in human defences.
Beren Aylan, joint first author and PhD student at the Crick together with Elliott Bernard and Enrica Pellegrino, said: “Antibiotic resistance is a huge threat to our health so it’s incredibly important to understand how our bodies fight infection and where there might be room for improvement.
“TB is a great example of where targeting our own immune defences could be really effective, because it takes a very long course of different antibiotic treatments to effectively remove the infection. Anything that can be done to more effectively remove bacteria, could also make a huge difference to the cost and accessibility of treatments.”
The team are now planning to screen for drug compounds that could be used to boost autophagy in a targeted way.
“Boosting the autophagy pathway isn’t as simple as it might seem,” adds Max. This is because all parts of the body use autophagy as a way to recycle old and damaged cells. In order to safely increase autophagy in the location of infections, we need to target the pathway in macrophages alone.”