title: The human apoptosis inhibitor NAIP induces pyroptosis in macrophages infected with Legionella pneumophila.
abstract: Human nucleotide oligomerization domain-like receptor family apoptosis inhibitory protein (NAIP) prevents apoptosis by inhibiting caspase-3, -7, and -9. Four functional Naip exist in the murine genome, each of which is equally similar to human NAIP. Among them, Naip5 induces pyroptosis by promoting caspase-1 activation in response to Legionella pneumophila infection in macrophages. However, the contribution of human NAIP to this response is unclear. To investigate the role of human NAIP in macrophage survival, we stably expressed human NAIP in RAW264.7 macrophages. Human NAIP inhibited camptothecin-induced apoptosis in macrophages; however, it promoted cytotoxicity in L. pneumophila-infected cells. This cytotoxicity was associated with caspase-1. In addition, human NAIP restricted the intracellular growth of L. pneumophila. L. pneumophila flagellin was required for cytotoxicity, caspase-1 activation, and restriction of intracellular bacterial growth. Expression of murine Naip5 produced comparable results. These data indicate that human NAIP regulates the host response to L. pneumophila infection in a manner similar to that of murine Naip5 and that human NAIP and murine Naip5 regulate cell survival by inhibiting apoptosis or by promoting pyroptosis in response to specific cellular signals.
authors.affiliation: Division of Microbiology, Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Japan.
authors.forename: Nanako
authors.initials: N
authors.lastname: Katagiri
authors.forename: Takeo
authors.initials: T
authors.lastname: Shobuike
authors.forename: Bin
authors.initials: B
authors.lastname: Chang
authors.forename: Akiko
authors.initials: A
authors.lastname: Kukita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000009:adverse effects; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004789:Enzyme Activation; D005408:Flagellin / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D016952:Legionella pneumophila / Q000254:growth & development* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D061945:Caspase Inhibitors; D053583:Interleukin-1beta; C496800:NAIP protein, human; C496806:Naip5 protein, mouse; D051616:Neuronal Apoptosis-Inhibitory Protein; D011993:Recombinant Fusion Proteins; D005408:Flagellin; D020170:Caspase 1; D002166:Camptothecin