Interferon-gamma reverses the evasion of Birc1e/Naip5 gene mediated murine macrophage immunity by Legionella pneumophila mutant lacking flagellin.
Legionella pneumophila is the etiologic agent of Legionnaires' disease. This bacterium contains a single monopolar flagellum, of which the FlaA subunit is a major protein constituent. The murine macrophage resistance against this bacterium is controlled by the Birc1e/Naip5 gene, which belongs to the NOD family. We evaluated the intracellular growth of the flaA mutant bacteria as well as another aflagellated fliA mutant, within bone marrow-derived macrophages from mice with an intact (C57BL/6, BALB/c) or mutated (A/J) Birc1e/Naip5 gene. The flaA mutant L. pneumophila multiplied within C57BL/6 and BALB/c macrophages while the wild-type strain did not. Cell viability was not impaired until 3 days after infection when the flaA mutant bacteria replicated 10(2-3)-fold in macrophages, implying that L. pneumophila inhibited host cell death during the early phase of intracellular replication. The addition of recombinant interferon-gamma (IFN-gamma) to the infected macrophages restricted replication of the flaA mutant within macrophages; these treated cells also showed enhanced nitric oxide production, although inhibition of nitric oxide production did not affect the IFN-gamma induced inhibition of Legionella replication. These findings suggested that IFN-gamma activated macrophages to restrict the intracellular growth of the L. pneumophila flaA mutant by a NO independent pathway.
Akamine
Morikazu
M
Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. h066567@eve.u-ryukyu.ac.jp
Higa
Futoshi
F
Haranaga
Syusaku
S
Tateyama
Masao
M
Mori
Naoki
N
Heuner
Klaus
K
Fujita
Jiro
J
D000818:Animals; D005408:Flagellin / Q000235:genetics / Q000276:immunology*; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D016952:Legionella pneumophila / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000235:genetics / Q000276:immunology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011994:Recombinant Proteins
D007370:Interferon Type I; D053762:Interleukin-12 Subunit p40; C496806:Naip5 protein, mouse; D051616:Neuronal Apoptosis-Inhibitory Protein; D011994:Recombinant Proteins; D005408:Flagellin; C067138:flaA protein, bacteria; D009569:Nitric Oxide; D007371:Interferon-gamma