Manipulation of the host by pathogens to survive the lysosome

Abstract Lysosomes form part of our innate immunity and are an important line of defence against microbes, viruses and parasites. Although it is more than 50 years since de Duve discovered lysosomes, it is only in more recent years that we are slowly unravelling the molecular mechanisms involved in the delivery of material to the lysosome. However, successful intracellular pathogens often have a better grip on the mechanisms involved in delivery to the lysosome and can manipulate membrane trafficking pathways to create an intracellular environment that is favourable for replication. By studying pathogen effector proteins that are secreted into the host's cytosol, we can learn about both pathogen-survival mechanisms and further regulatory elements involved in trafficking to the lysosome. Lysosomal evasion There is a major advantage for a pathogen to gain entry into cells and that is hiding itself from our immune system yet receiving nutrients from the infected cell. However, an intracellular location still has some pitfalls that need to be avoided. If you are phagocytosed, then the end point of the phagocytic pathway is the formation of the phagolysosome and therefore delivery to the hydrolytic environment of the lysosome. To survive this environment, there are various options. One is to opt out of the final destination; for instance, Listeria monocytogenes and Shigella spp. rapidly lyse the phagosomal membrane and escape into the host's cytosol Key words: endocytosis, endosome, lysosome, pathogen, phagocytosis, phagolysosome. Abbreviations used: CPY, carboxypeptidase-Y; ER, endoplasmic reticulum; ESCRT, endosomal sorting complex required for transport; HOPS, homotypic fusion and vacuole protein sorting; RILP, Rab7-interacting lysosomal protein; SNARE, soluble N-ethylmaleimide-sensitive factorattachment protein receptor; VAMP8, vesicle-associated membrane protein 8; Vps, vacuolar protein sorting