The immunity-related p47 guanosine triphosphatases are a class of innate immunity effectors found in murine cells, where they play a role in defense against intracellular pathogens. However, the role of similar proteins in humans has been less clear. Now Singh et al. demonstrate that in mouse cells one of these receptors acts via autophagy, inducing large autolysosomal organelles to destroy intracellular Mycobacterium tuberculosis bacilli. Furthermore, the sole human counterpart, IRGM, also works via autophagy to control intracellular mycobacteria.