Evolving immunity: Xenophagy and the removal of intracellular pathogens

Early eukaryotes, such as free-living protozoa and yeasts, had to adapt to rapidly changing environments and an uncertain food supply. Lack of food imposed serious stress on these cells and it is thought that this drove the evolution of a membrane trafficking pathway called autophagy. Autophagy allows cells to deliver cytosolic proteins and organelles to lysosomes for degradation and provides a short-term supply of amino acids. Autophagy allowed early eukaryotes to generate the amino acids they needed to move and search for food and provided an advantage over sedentary cells that generated spores during famine. The capacity to degrade large quantities of cytoplasm also provided these early cells with a powerful mechanism to degrade intracellular pathogens. When autophagy engulfs pathogens the pathway is called ‘xenophagy’ because delivery to lysosomes leads to the removal of foreign organisms1. Xenophagy therefore represents a very early stage in the evolution of innate immunity.