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Interferon‐Gamma Reverses the Evasion of Birc1e/Naip5 Gene Mediated Murine Macrophage Immunity by Legionella pneumophila Mutant Lacking Flagellin
Author(s) -
Akamine Morikazu,
Higa Futoshi,
Haranaga Syusaku,
Tateyama Masao,
Mori Naoki,
Heuner Klaus,
Fujita Jiro
Publication year - 2007
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2007.tb03909.x
Subject(s) - legionella pneumophila , biology , flagellin , microbiology and biotechnology , mutant , macrophage , intracellular parasite , interferon gamma , intracellular , virology , bacteria , immune system , gene , in vitro , immunology , biochemistry , genetics
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‐γ) 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‐γ induced inhibition of Legionella replication. These findings suggested that IFN‐γ activated macrophages to restrict the intracellular growth of the L. pneumophila flaA mutant by a NO independent pathway.