which can lead to infection after prolonged exposure. Frequency of occurrence In the United States, approximately 3 infections with L. pneumophila appear per 100,000 people per year. The infections peak in the summer. Within endemic regions, about 4% to 5% of pneumonia cases are caused by L. pneumophila. Pathogenesis In humans, L. pneumophila invades and replicates inside macrophages. The internalization of the bacteria can be enhanced by the presence of antibody and complement, but is not absolutely required. Internalization of the bacteria appears to occur through phagocytosis. However, L. pneumophila is also capable of infecting non-phagocytic cells through an unknown mechanism. A rare form of phagocytosis known as coiling phagocytosis has been described for L. pneumophila, but this is not dependent on the Dot/Icm (intracellular multiplication/defect in organelle trafficking genes) bacterial secretion system and has been observed for other pathogens. Once internalized, the bacteria surround themselves in a membrane-bound vacuole that does not fuse with lysosomes that would otherwise degrade the bacteria. In this protected compartment, the bacteria multiply. Dot/Icm type IV secretion system and effector proteins The bacteria use a type IVB secretion system known as Dot/Icm to inject effector proteins into the host. These effectors are involved in increasing the bacteria's ability to survive inside the host cell. L. pneumophila encodes for over 330 "effector" proteins, which are secreted by the Dot/Icm translocation system to interfere with host cell processes to aid bacterial survival. It has been predicted that the genus Legionella encodes more than 10,000 and possibly up to ~18,000 effectors that have a high probability to be secreted into their host cells. One key way in which L. pneumophila uses its effector proteins is to interfere with fusion of the Legionella-containing vacuole with the host's endosomes, and thus protect against lysis. Knock-out studies of Dot/Icm translocated effectors indicate that they are vital for the intracellular survival of the bacterium, but many individual effector proteins are thought to function redundantly, in that single-effector knock-outs rarely impede intracellular survival. This high number of translocated effector proteins and their redundancy is likely a result of the bacterium having evolved in many different protozoan hosts. Legionella-containing vacuole For Legionella to survive within macrophages and protozoa, it must create a specialized compartment known as the Legionella-containing vacuole (LCV). Through the action of the Dot/Icm secretion system, the bacteria are able to prevent degradation by the normal endosomal trafficking pathway and instead