Scientists discover ‘hidden switch’ in immune cells that helps the body kill deadly fungus

Researchers at the University of East Anglia (UEA) discovered that the protein RAB5c is critical for immune cells to kill *Aspergillus fumigatus*, a deadly fungus causing lung infections in immunocompromised patients. The study, involving the Babraham Institute and Universidade de Sao Paulo, found that without RAB5c, macrophages fail to properly deploy toxic molecules, allowing the fungus to survive despite immune attacks." "article": "Scientists at the University of East Anglia’s Norwich Medical School identified the protein RAB5c as a key regulator in immune cells’ ability to destroy *Aspergillus fumigatus*, a fungus responsible for fatal lung infections in vulnerable patients. The fungus, commonly inhaled daily, poses severe risks to cancer patients, transplant recipients, and those with lung diseases, killing tens of thousands annually. The research, conducted with the Babraham Institute and Universidade de Sao Paulo, used gene silencing to observe immune cell behavior. When macrophages—immune cells that engulf pathogens—lacked RAB5c, they failed to deliver lethal molecules to fungal spores, even if producing toxic oxygen radicals. RAB5c acts as a traffic controller, ensuring the phagosome (a compartment where spores are trapped) acidifies and deploys enzymes to kill the fungus. Mice lacking the RAB5c pathway showed higher fungal loads, lung damage, and inflammation, while those with functional RAB5c cleared infections more effectively. The findings suggest current immune responses may fail due to misdirected toxicity rather than weak aggression. The discovery could lead to new treatments by enhancing patients’ immune machinery rather than directly targeting the fungus. Since the same pathway fights viruses and bacteria, the research may also apply to broader infectious diseases and inflammation control.