Legionnaires’ disease and its agent Legionella pneumophila

Legionella pneumophila, the agent responsible for Legionnaire?s disease, is a facultative intracellular pathogen that can replicate within protozoa and macrophages. Protozoa are considered to play a central role in the pathogenesis and ecology ofL. pneumophila. In humans,L. pneumophilareaches the lungs, where it is ingested by alveolar macrophages. Unlike phagosomes containing inert particles or avirulent bacteria, theL. pneumophila-containing vacuoles avoid fusion with lysosomes, recruiting rough endoplasmic reticulum and mitochondria. The formation of this specialized vacuole is directed by the type IV secretion system encoded by thedot/icmgenes in mammalian and protozoan cells. Killing of mammalian cells byL. pneumophilahas been proposed to occur through induction of apoptosis during the early stages of the infection. A rapid induction of necrosis by L.pneumophilaalso occurs upon entry into the post-exponential phase of growth within both macrophages and protozoa, when the bacteria become cytotoxic. Before the lysis of the mammalian or protozoan plasma membrane, the bacteria egress into the cytoplasm.In vivo, clearance ofLegionellafrom the lungs depends on the host production of IFN-?in A/J mice, while in BALB/c mice IFN-?is not produced. Intracellular replication ofL. pneumophilais inhibited in IFN-?-activated mouse and human primary macrophages. Both antigen-specific humoral and cell-mediated immune responses are induced duringLegionellainfection. AlthoughLegionella-specific antibodies are produced during human or murine infection, acquired cell-mediated immune response is believed to play a stronger role inLegionellaclearance. Both macrophages and DCs are able to present microbial antigens on major histocompatibility class I and class II molecules, which stimulate antigen-specific T-cell response. Identification of antigens and determination of vesicular trafficking mechanisms involved in processing and presentation remain to be understood in greater detail.