The pathogenesis of Legionella infections begins with a supply of water containing virulent bacteria and with a means for dissemination to humans (Fig. 40-1). Person-to-person transmission has never been demonstrated, and Legionella is not a member of the bacterial flora of humans.
The usual tissue culture media, which are adequate to support the growth of human and animal cells, cannot support the growth of Legionella cells. The bacteria also grow well within alveolar macrophages that have been maintained in cell culture. If phagocytosis is prevented by treatment with cytochalasin, however, the bacteria are denied access to the intracellular environment and growth does not occur.
). The bacteria bind to alveolar macrophages via the complement receptors and are engulfed into a phagosomal vacuole. However, by an unknown mechanism, the bacteria block the fusion of lysosomes with the phagosome, preventing the normal acidification of the phagolysosome and keeping the toxic myeloperoxidase system segregated from the susceptible bacteria. The bacilli multiply within the phagosome. Thus, a cellular compartment that should be a death trap instead becomes a nursery. Eventually, the cell is destroyed, releasing a new generation of microbes to infect other cells.
Exponential bacterial growth begins soon after infection at a time when only macrophages are present; bacteria are most numerous 3 to 4 days later, but have virtually disappeared by the end of the first week. Infection elicits a large influx of polymorphonuclear leukocytes, followed by monocytes from the peripheral blood. Fluid exudation into the alveoli follows the pattern of the polymorphonuclear leukocytes. Specific immunologic responses (i.e., antibody and lymphocyte influx) are detectable 4 to 5 days after infection.
The air spaces are filled with fibrin and inflammatory cells. The consistency of the completely consolidated lower lobe (C) resemble that of an adjacent hilar lymph node (N). The lobular nature of the process is accentuated by gray carbon accumulation around the terminal bronchioles in the centers of the lobules (L).
). Leaky capillaries allow the transudation of serum and deposition of fibrin in the alveoli. The result is a destructive pneumonia that obliterates the air spaces and compromises respiratory function (Fig. 40-5). Dissemination of bacteria to sites outside the lung occurs at least partially via macrophages, but only rarely does an inflammatory response develop.
The symptoms of Legionella infection undoubtedly result from a combination of physical interference with oxygenation of blood, ventilation-perfusion imbalance in the remaining lung tissue, and release of toxic products from bacteria and inflammatory cells. Bacterial factors include a protease that may be responsible for tissue damage. Cellular factors include interleukin-1, which produces fever after it is released from monocytes, and tumor necrosis factor, which may be responsible for some of the systemic symptoms.
Virulence appears to be multifactorial. An outer membrane protein that functions as a metalloprotease and a cytoplasmic membrane heat-shock protein elicit protective immune responses, but are not essential for expression of virulence. A gene that encodes a 29 Kd protein and plays a role in cellular infection has been identified. Mutations of the gene are associated with decreased virulence.
