Home LiteratureArticle Details
PMID: 9916101 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Apoptosis in macrophages and alveolar epithelial cells during early stages of infection by Legionella pneumophila and its role in cytopathogenicity.

Infection and immunity ·Vol. 67 ·No. 2 ·1999-02-00 ·Pages 862-70

Gao LY, Abu Kwaik Y

Abstract

The hallmark of Legionnaires' disease is intracellular replication of Legionella pneumophila within cells in the alveolar spaces. Cytopathogenicity of this bacterium to the host cell has been well demonstrated, but the mechanisms of host cell death due to infection by L. pneumophila are not well understood. In this study, induction of apoptosis in macrophages and alveolar epithelial cells by L. pneumophila during early stages of infection was confirmed by using multiple criteria, including DNA fragmentation by agarose gel electrophoresis, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, surface exposure of phosphatidylserine, and cellular morphology by transmission electron microscopy. Induction of nuclear apoptosis in L. pneumophila-infected macrophages is mediated by activation of the caspase cascade death machinery. We provide genetic and biochemical evidence that L. pneumophila-induced apoptosis in macrophages and alveolar epithelial cells does not require intracellular bacterial replication or new protein synthesis. In addition, extracellular L. pneumophila is capable of inducing apoptosis. Furthermore, induction of apoptosis by L. pneumophila correlates with cytopathogenicity. We conclude that L. pneumophila-induced apoptosis in macrophages and alveolar epithelial cells plays an important role in cytopathogenicity to the host cell during early stages of infection.

MeSH Terms
Amino Acid Chloromethyl Ketones/pharmacology Apoptosis Cysteine Proteinase Inhibitors/pharmacology Enzyme Activation Epithelial Cells/microbiology,pathology Extracellular Space Humans Intracellular Fluid Legionella pneumophila/physiology Macrophages/microbiology,pathology Protein Biosynthesis U937 Cells
Chemicals
Amino Acid Chloromethyl Ketones Cysteine Proteinase Inhibitors benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gao L Y
Department of Microbiology and Immunology, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0084, USA.
Abu Kwaik Y
References (40)
40 references, click to expand
  1. Fatal attraction of mammalian cells to Legionella pneumophila.
    Mol Microbiol. 1998 Nov;30(4):689-95 PMID: 10094618
  2. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
    J Cell Biol. 1992 Nov;119(3):493-501 PMID: 1400587
  3. Shigella flexneri induces apoptosis in infected macrophages.
    Nature. 1992 Jul 9;358(6382):167-9 PMID: 1614548
  4. Legionella pneumophila inhibits protein synthesis in Chinese hamster ovary cells.
    Infect Immun. 1991 Jan;59(1):240-6 PMID: 1987039
  5. Effects of cytochalasin D and methylamine on intracellular growth of Legionella pneumophila in amoebae and human monocyte-like cells.
    Infect Immun. 1991 Mar;59(3):758-63 PMID: 1997428
  6. Induction of apoptosis (programmed cell death) in human leukemic HL-60 cells by inhibition of RNA or protein synthesis.
    J Immunol. 1990 Sep 15;145(6):1859-67 PMID: 2167911
  7. Growth of Legionella pneumophila in a human macrophage-like (U937) cell line.
    Microb Pathog. 1988 Aug;5(2):87-95 PMID: 3237054
  8. The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes.
    J Exp Med. 1983 Dec 1;158(6):2108-26 PMID: 6644240
  9. Cell number and cell characteristics of the normal human lung.
    Am Rev Respir Dis. 1982 Jun;125(6):740-5 PMID: 7091881
  10. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl.
    J Exp Med. 1995 Nov 1;182(5):1545-56 PMID: 7595224
  11. Infectivity of Legionella pneumophila mip mutant for alveolar epithelial cells.
    Curr Microbiol. 1995 Apr;30(4):247-50 PMID: 7765898
  12. Cloning and molecular characterization of a Legionella pneumophila gene induced by intracellular infection and by various in vitro stress conditions.
    Mol Microbiol. 1994 Jul;13(2):243-51 PMID: 7984104
  13. Cytotoxicity of extracellular Legionella pneumophila.
    Infect Immun. 1994 May;62(5):2111-4 PMID: 8168978
  14. Phenotypic modulation by Legionella pneumophila upon infection of macrophages.
    Infect Immun. 1993 Apr;61(4):1320-9 PMID: 8454334
  15. Apoptosis.
    Immunol Today. 1993 Mar;14(3):126-30 PMID: 8466628
  16. Legionella pneumophila replicates within rat alveolar epithelial cells.
    J Infect Dis. 1993 May;167(5):1138-45 PMID: 8486946
  17. Elevated levels of Legionella pneumophila stress protein Hsp60 early in infection of human monocytes and L929 cells correlate with virulence.
    Infect Immun. 1996 Jun;64(6):1968-76 PMID: 8675295
  18. Salmonella typhimurium invasion induces apoptosis in infected macrophages.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9833-8 PMID: 8790417
  19. The use of differential display-PCR to isolate and characterize a Legionella pneumophila locus induced during the intracellular infection of macrophages.
    Mol Microbiol. 1996 Aug;21(3):543-56 PMID: 8866478
  20. Evidence for apoptosis of human macrophage-like HL-60 cells by Legionella pneumophila infection.
    Infect Immun. 1996 Dec;64(12):4900-6 PMID: 8945524
  21. Inhibition of Ced-3/ICE-related proteases does not prevent cell death induced by oncogenes, DNA damage, or the Bcl-2 homologue Bak.
    J Cell Biol. 1997 Jan 13;136(1):215-27 PMID: 9008715
  22. Topology of Legionella pneumophila DotA: an inner membrane protein required for replication in macrophages.
    Infect Immun. 1997 Feb;65(2):571-8 PMID: 9009315
  23. Purification and characterization of Mycoplasma penetrans Ca2+/Mg2+-dependent endonuclease.
    J Bacteriol. 1997 Apr;179(7):2210-20 PMID: 9079906
  24. Kinase cascades regulating entry into apoptosis.
    Microbiol Mol Biol Rev. 1997 Mar;61(1):33-46 PMID: 9106363
  25. Apoptosis as a proinflammatory event: what can we learn from bacteria-induced cell death?
    Trends Microbiol. 1997 May;5(5):201-4 PMID: 9160509
  26. Transcriptional regulation of the macrophage-induced gene (gspA) of Legionella pneumophila and phenotypic characterization of a null mutant.
    Mol Microbiol. 1997 May;24(3):629-42 PMID: 9179855
  27. Utilization of similar mechanisms by Legionella pneumophila to parasitize two evolutionarily distant host cells, mammalian macrophages and protozoa.
    Infect Immun. 1997 Nov;65(11):4738-46 PMID: 9353059
  28. Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis.
    Infect Immun. 1997 Nov;65(11):4813-21 PMID: 9353070
  29. Caspases: intracellular signaling by proteolysis.
    Cell. 1997 Nov 14;91(4):443-6 PMID: 9390553
  30. Induced expression of the Legionella pneumophila gene encoding a 20-kilodalton protein during intracellular infection.
    Infect Immun. 1998 Jan;66(1):203-12 PMID: 9423859
  31. Conjugative transfer by the virulence system of Legionella pneumophila.
    Science. 1998 Feb 6;279(5352):873-6 PMID: 9452389
  32. Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation.
    J Exp Med. 1998 Feb 16;187(4):487-96 PMID: 9463399
  33. Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome.
    Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1669-74 PMID: 9465074
  34. Evidence for pore-forming ability by Legionella pneumophila.
    Mol Microbiol. 1998 Jan;27(2):323-36 PMID: 9484888
  35. Identification of macrophage-specific infectivity loci (mil) of Legionella pneumophila that are not required for infectivity of protozoa.
    Infect Immun. 1998 Mar;66(3):883-92 PMID: 9488371
  36. Expression of multiple pili by Legionella pneumophila: identification and characterization of a type IV pilin gene and its role in adherence to mammalian and protozoan cells.
    Infect Immun. 1998 Apr;66(4):1768-75 PMID: 9529112
  37. NF-kappa B-dependent inhibition of apoptosis is essential for host cellsurvival during Rickettsia rickettsii infection.
    Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4646-51 PMID: 9539792
  38. Expression of Legionella pneumophila virulence traits in response to growth conditions.
    Infect Immun. 1998 Jul;66(7):3029-34 PMID: 9632562
  39. Invasion of protozoa by Legionella pneumophila and its role in bacterial ecology and pathogenesis.
    Appl Environ Microbiol. 1998 Sep;64(9):3127-33 PMID: 9726849
  40. Different fates of Legionella pneumophila pmi and mil mutants within macrophages and alveolar epithelial cells.
    Microb Pathog. 1998 Dec;25(6):291-306 PMID: 9895268
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.67.2.862-870.1999
Published
1999-02-00
Pages
862-70
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC96397
Subset
IM
Grants
NIAID NIH HHS · R29AI-38410 · United States
External Links
PubMed source DOI: 10.1128/IAI.67.2.862-870.1999 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2