title: Apoptosis-associated speck-like protein (ASC) controls Legionella pneumophila infection in human monocytes.
abstract: 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.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Center for Microbial Interface Biology and the Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Dalia H
authors.initials: DH
authors.lastname: Abdelaziz
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Gavrilin
authors.forename: Anwari
authors.initials: A
authors.lastname: Akhter
authors.forename: Kyle
authors.initials: K
authors.lastname: Caution
authors.forename: Sheetal
authors.initials: S
authors.lastname: Kotrange
authors.forename: Arwa Abu
authors.initials: AA
authors.lastname: Khweek
authors.forename: Basant A
authors.initials: BA
authors.lastname: Abdulrahman
authors.forename: Jaykumar
authors.initials: J
authors.lastname: Grandhi
authors.forename: Zeinab A
authors.initials: ZA
authors.lastname: Hassan
authors.forename: Clay
authors.initials: C
authors.lastname: Marsh
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wewers
authors.forename: Amal O
authors.initials: AO
authors.lastname: Amer
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D020170:Caspase 1; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D007877:Legionnaires' Disease / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000382:microbiology*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D016328:NF-kappa B; C435692:NLRC4 protein, human; C402202:PYCARD protein, human; D020170:Caspase 1