Bacteria of Legionella species cause two primary human diseases: Legionella pneumonia (often referred to as Legionnaires’ disease) and Pontiac fever; collectively, these diseases are referred to as legionellosis. Legionnaires’ disease was first described in 1976 in an outbreak among members of the American Legion participating in a conference at a hotel in Philadelphia, Pennsylvania. Since their original description, Legionella-related infections have increased in frequency throughout the world as techniques to diagnose them have improved, clinical awareness has increased, cities have grown, and water systems have both aged and become more complex. Most cases of legionellosis are linked to waterborne exposures. These infections can be either sporadic or due to common-source community or nosocomial exposures. Outbreaks of legionellosis are well described. After exposure, legionellosis occurs primarily among persons with risk factors for disease, including older adults and those with primary organ dysfunction, immunocompromise, or other chronic illnesses. Clinical awareness is important, as the similarity of signs and symptoms of legionellosis to those of other respiratory illnesses can lead to delayed treatment. Despite appropriate therapy, Legionella pneumonia is associated with significant morbidity and mortality.
PATHOGEN AND PATHOGENICITY
Legionellae are aerobic gram-negative bacteria that are ubiquitous in aquatic environments, damp soil, and compost. Of the more than 60 Legionella species, approximately half have been documented to lead to clinical disease, but most clinical disease is driven by Legionella pneumophila, primarily serotype 1. The primary habitats for growth and replication of Legionella are amoebae and other free-living protozoa, in which these bacterial species can thrive intracellularly; humans are accidental hosts. Legionellae are reliant on host-derived amino acids and nutrients for intracellular replication. The organisms have a biphasic life cycle: a replicative phase in nutrient-rich conditions (e.g., in their protozoal hosts) and a noninfective transmissive phase under scarcity of resources. Therefore, they can persist in complex biofilms in both natural and engineered water systems (e.g., premise plumbing—a building’s hot and cold water piping systems) and are phagocytized by waterborne protozoa. In premise plumbing systems, where temperature and nutrients support the protozoal hosts of legionellae, the bacteria can replicate to concentrations sufficient to cause human infection.
After exposure to Legionella through inhalation or aspiration of small aerosol particles, the organisms attach to immune cells and are phagocytized. After phagocytosis, they can evade intracellular defenses and replicate in human alveolar macrophages and monocytes. Pathogenic Legionella species have numerous virulence systems that they use to evade the human immune system, including the development of Legionella-containing vacuoles within immune cells, downregulation of cytokine receptors, inhibition of host protein synthesis, and avoidance of lysosomal degradation. Despite their ability to replicate and persist in the intracellular environment, innate immune components that target intracellular pathogens—specifically, pattern recognition receptors, including Toll-like receptors and nucleotide-binding oligomerization domain–like receptors—activate immune responses. Adaptive CD4 and CD8 cytotoxic T-cell involvement and these innate immune responses eventually lead to the production of interferon γ ...