Legionella pneumophila Replicates within Rat Alveolar Epithelial Cells

Mody, Christopher H.; Paine, Robert; Shahrabadi, M Shamsi; Simon, Richard H.; Pearlman, Eric; Eisenstein, Barry I.; Toews, Galen B.

doi:10.1093/infdis/167.5.1138

Cited by 71 publications

(56 citation statements)

References 32 publications

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“…In particular, alveolar epithelial cell apoptosis may be crucial for initiation of enhanced pulmonary permeability because these cells cover Ͼ95% of alveolar air space and are paramount in maintaining the integrity of the alveolar-capillary barrier (37). In addition, because Legionella has a strong predilection for invasion of alveolar epithelial cells (9,13,14), bacterial cytotoxicity, in combination with host factors (e.g., TNF-␣), may be pivotal to the development of epithelial injury, acute lung damage, and increased mortality in Legionella pneumonia. Our in vitro experiments mimicking in vivo hyperoxia support a direct effect of hyperoxia as a mediator of alveolar epithelial cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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Hyperoxia Mediates Acute Lung Injury and Increased Lethality in MurineLegionellaPneumonia: The Role of Apoptosis

Tateda

Deng

Moore

et al. 2003

The Journal of Immunology

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Legionella pneumophila is a major cause of life-threatening pneumonia, which is characterized by a high incidence of acute lung injury and resultant severe hypoxemia. Mechanical ventilation using high oxygen concentrations is often required in the treatment of patients with L. pneumophila pneumonia. Unfortunately, oxygen itself may propagate various forms of tissue damage, including acute lung injury. The effect of hyperoxia as a cofactor in the course of L. pneumophila pneumonia is poorly understood. In this study, we show that exposure to hyperoxic conditions during the evolution of pneumonia results in a marked increase in lethality in mice with Legionella pneumonia. The enhanced lethality was associated with an increase in lung permeability, but not changes in either lung bacterial burden or leukocyte accumulation. Interestingly, accelerated apoptosis as evidenced by assessment of histone-DNA fragments and caspase-3 activity were noted in the infected lungs of mice exposed to hyperoxia. TUNEL staining of infected lung sections demonstrated increased apoptosis in hyperoxic mice, predominantly in macrophages and alveolar epithelial cells. In vitro exposure of primary murine alveolar epithelial cells to Legionella in conjunction with hyperoxia accelerated apoptosis and loss of barrier function. Fas-deficient mice demonstrated partial resistance to the lethal effects of Legionella infection induced by hyperoxia, which was associated with attenuated apoptosis in the lung. These results demonstrate that hyperoxia serves as an important cofactor for the development of acute lung injury and lethality in L. pneumophila pneumonia. Exaggerated apoptosis, in part through Fas-mediated signaling, may accelerate hyperoxia-induced acute lung injury in Legionella pneumonia.

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Section: Discussionmentioning

confidence: 99%

“…In lung tissue, bacteria multiply in several types of host cells, including macrophages, monocytes, and alveolar epithelial cells (7)(8)(9). Cytopathogenicity of L. pneumophila to host cells has been well demonstrated (10 -12), although incompletely understood.…”

mentioning

confidence: 99%

Hyperoxia Mediates Acute Lung Injury and Increased Lethality in MurineLegionellaPneumonia: The Role of Apoptosis

Tateda

Deng

Moore

et al. 2003

The Journal of Immunology

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“…Macrophages are the primary cell type that L. pneumophila replicates within during infection (Davis et al, 1983 ;Winn & Myerowitz, 1981), but it has been suggested that epithelial cells may also play a role (Mody et al, 1993). In addition to the conventional phagocytic mechanism observed in most organisms, entry of L. pneumophila into monocytes has been shown to occur by an unusual mechanism termed ' coiling phagocytosis ' (Cirillo et al, 1994 ;Horwitz, 1984 ;Rechnitzer & Blom, 1989).…”

Section: Abbreviationsmentioning

confidence: 99%

Identification of novel loci involved in entry by Legionella pneumophila The GenBank accession numbers for the enh1 and enh2 loci reported in this paper are AF057703 and AF057704, respectively.

2000

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Legionella pneumophila is primarily an intracellular pathogen during infection ; thus, the mechanisms of entry into host cells are likely to be important for pathogenesis. Several L. pneumophila mutants that display an enhanced-entry (Enh) phenotype were isolated by selecting for bacteria that enter host cells at a higher frequency than wild-type. In the course of characterizing the genetic basis of one of these mutants, C3, a strategy was developed for the isolation of laboratory-media-repressed virulence determinants from L. pneumophila. Screens for dominant mutations using a genomic DNA library from C3 resulted in the isolation of three cosmids that confer an Enh phenotype to wild-type L. pneumophila. Transposon mutagenesis of these cosmids allowed identification of three loci that affect entry. Analysis of the putative proteins encoded by these loci, designated rtxA and enhC, demonstrated similarity to repeats in the structural toxin protein and the secreted Sel-1 protein from Caenorhabditis elegans, respectively. L. pneumophila rtxA and enhC mutants display significantly reduced entry into host cells, compared to wild-type bacteria. The phenotype that the cosmids containing these loci confer is most likely due to elevated expression resulting from their presence on multicopy vectors. The use of increased gene copy number to overexpress genes that are normally repressed under laboratory growth conditions is generally applicable to the isolation of virulence determinants from L. pneumophila and other bacterial pathogens.

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“…Pulmonary alveolar epithelial cells may represent an alternative site for replication of Legionella species in the terminal airspace and thus clarify some previously unexplained aspects of the pathogenesis of Legionnaires' disease (Mody et al, 1993). Legionella dumof®i has an ability to invade and proliferate in human alveolar epithelial cells, which may explain the rapid and fulminant progress of the pneumonia it causes.…”

Section: Protozoa and Pathology Of Legionellosismentioning

confidence: 99%

Legionella: from environmental habitats to disease pathology, detection and control

Atlas

1999

Environmental Microbiology

209

148

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Studies on Legionella show a continuum from environment to human disease. Legionellosis is caused by Legionella species acquired from environmental sources, principally water sources such as cooling towers, where Legionella grows intracellularly in protozoa within biofilms. Aquatic biofilms, which are widespread not only in nature, but also in medical and dental devices, are ecological niches in which Legionella survives and proliferates and the ultimate sources to which outbreaks of legionellosis can be traced. Invasion and intracellular replication of L. pneumophila within protozoa in the environment play a major role in the transmission of Legionnaires' disease. Protozoa provide the habitats for the environmental survival and reproduction of Legionella species. L. pneumophila proliferates intracellularly in various species of protozoa within vacuoles studded with ribosomes, as it also does within macrophages. Growth within protozoa enhances the environmental survival capability and the pathogenicity (virulence) of Legionella. The growth requirements of Legionella, the ability of Legionella to enter a viable non‐culturable state, the association of Legionella with protozoa and the occurrence of Legionella within biofilms complicates the detection of Legionella and epidemiological investigations of legionellosis. Polymerase chain reaction (PCR) methods have been developed for the molecular detection of Legionella and used in environmental and epidemiological studies. Various physical and chemical disinfection methods have been developed to eliminate Legionella from environmental sources, but gaining control of Legionella in environmental waters, where they are protected from disinfection by growing within protozoa and biofilms, remains a challenge, and one that must be overcome in order to eliminate sporadic outbreaks of legionellosis.

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Legionella pneumophila Replicates within Rat Alveolar Epithelial Cells

Cited by 71 publications

References 32 publications

Hyperoxia Mediates Acute Lung Injury and Increased Lethality in MurineLegionellaPneumonia: The Role of Apoptosis

Hyperoxia Mediates Acute Lung Injury and Increased Lethality in MurineLegionellaPneumonia: The Role of Apoptosis

Identification of novel loci involved in entry by Legionella pneumophila The GenBank accession numbers for the enh1 and enh2 loci reported in this paper are AF057703 and AF057704, respectively.

Legionella: from environmental habitats to disease pathology, detection and control

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