The infection enigma: why some people die from typically harmless germs

"Michael Levin had just started working as a paediatric infectious-disease doctor in London when he received an urgent call from a hospital in Malta. It was the early 1980s, and a young boy had been brought in with symptoms of a severe infection that was spreading through his body, damaging multiple organs and tissues. But his doctors could find no trace of a pathogen."

"Not long after that, a group in France discovered that similar mutations were responsible for rare cases of severe disease caused by another mycobacterial species - this time, a weakened form used as a tuberculosis vaccine. Researchers have since amassed a broad library of mutations in hundreds of genes that underlie 'inborn errors of immunity' (IEIs) and that make millions of people around the world susceptible to a wide range of infectious diseases and immune-linked ailments that many people can simply shrug off."

Some individuals suffer severe, even fatal, infections from microbes that rarely harm others because of inherited defects in immune genes. Family clusters of unusual infections revealed mutations such as defects in the interferon-γ receptor, impairing key immune signaling and inflammation control. A growing catalog of inborn errors of immunity spans hundreds of genes and explains susceptibility to diverse pathogens and immune-linked disorders in millions worldwide. Identifying these monogenic causes enables targeted diagnosis, tailored therapies, refined vaccine strategies and improved public-health responses by linking genetic variation with infection risk and clinical management.

Read at Nature