Apoptosis-associated Speck-like Protein (ASC) Controls Legionella pneumophila Infection in Human Monocytes

The ability of Legionella pneumophila to cause pneumonia is determined by its capability to evade the immune system and grow within human monocytes and their derived macrophages. Human monocytes efficiently activate caspase-1 in response to Salmonella but not to L. pneumophila. The molecular mechani...

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Bibliographic Details
Published in:The Journal of biological chemistry 2011-02, Vol.286 (5), p.3203-3208
Main Authors: Abdelaziz, Dalia H., Gavrilin, Mikhail A., Akhter, Anwari, Caution, Kyle, Kotrange, Sheetal, Khweek, Arwa Abu, Abdulrahman, Basant A., Grandhi, Jaykumar, Hassan, Zeinab A., Marsh, Clay, Wewers, Mark D., Amer, Amal O.
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis Regulatory Proteins
ASC
Calcium-Binding Proteins
CARD Signaling Adaptor Proteins
Caspase
Caspase 1
Cellular Immune Response
Cytoskeletal Proteins - immunology
Cytoskeletal Proteins - physiology
Human Monocytes
Humans
Immunology
Inflammasome
Inflammation
Innate Immunity
Legionella
Legionella pneumophila
Legionnaires' Disease - immunology
Monocytes - immunology
Monocytes - microbiology
NF-kappa B - metabolism
NOD-like Receptors
Salmonella
Signal Transduction
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Summary:The ability of Legionella pneumophila to cause pneumonia is determined by its capability to evade the immune system and grow within human monocytes and their derived macrophages. Human monocytes efficiently activate caspase-1 in response to Salmonella but not to L. pneumophila. The molecular mechanism for the lack of inflammasome activation during L. pneumophila infection is unknown. Evaluation of the expression of several inflammasome components in human monocytes during L. pneumophila infection revealed that the expression of the apoptosis-associated speck-like protein (ASC) and the NOD-like receptor NLRC4 are significantly down-regulated in human monocytes. Exogenous expression of ASC maintained the protein level constant during L. pneumophila infection and conveyed caspase-1 activation and restricted the growth of the pathogen. Further depletion of ASC with siRNA was accompanied with improved NF-κB activation and enhanced L. pneumophila growth. Therefore, our data demonstrate that L. pneumophila manipulates ASC levels to evade inflammasome activation and grow in human monocytes. By targeting ASC, L. pneumophila modulates the inflammasome, the apoptosome, and NF-κB pathway simultaneously.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M110.197681