Antibiotic use could be lessened after scientists discovered have macrophage activity is essential for tackling infections such as TB.
Researchers at the Francis Crick Institute, UK, say harnessing the immune system with new treatments could eventually help clinicians provide an alternative to antiobiotics – or improve their use.
Writing in Nature Microbiology, ahead of World TB Day on 24 March today, the team describe studying macrophages from induced pluripotent stem cells, which have the ability to become any cell type in the body.
Using genome editing tools to manipulate the macrophages’ ability to perform autophagy, they found when they removed the genes that are key to autophagy and infected the cells with Mycobacterium tuberculosis, the bacterial infection replicated more within the engineered cells. This led to mass host cell death.
The authors say this is evidence that autophagy plays a strong role in controlling intracellular infections, such as TB.
Dr Max Gutierrez, head of the Host-Pathogen Interactions in Tuberculosis Laboratory at the Crick, said: “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 validated its results using macrophages isolated from blood samples. It now plans 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,” said Dr Gutierrez. “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.”
Aylan B et al. ATG7 and ATG14 restrict cytosolic and phagosomal M. tuberculosis replication in human macrophages. Nature Microbiology 23 March 2023
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