{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T08:52:10Z","timestamp":1776329530892,"version":"3.50.1"},"reference-count":68,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,4,17]]},"abstract":"<jats:p>To restrict infection by Legionella pneumophila, mouse macrophages require Naip5, a member of the nucleotide-binding oligomerization domain leucine-rich repeat family of pattern recognition receptors, which detect cytoplasmic microbial products. We report that mouse macrophages restricted L. pneumophila replication and initiated a proinflammatory program of cell death when flagellin contaminated their cytosol. Nuclear condensation, membrane permeability, and interleukin-1\u03b2 secretion were triggered by type IV secretion-competent bacteria that encode flagellin. The macrophage response to L. pneumophila was independent of Toll-like receptor signaling but correlated with Naip5 function and required caspase 1 activity. The L. pneumophila type IV secretion system provided only pore-forming activity because listeriolysin O of Listeria monocytogenes could substitute for its contribution. Flagellin monomers appeared to trigger the macrophage response from perforated phagosomes: once heated to disassemble filaments, flagellin triggered cell death but native flagellar preparations did not. Flagellin made L. pneumophila vulnerable to innate immune mechanisms because Naip5+ macrophages restricted the growth of virulent microbes, but flagellin mutants replicated freely. Likewise, after intratracheal inoculation of Naip5+ mice, the yield of L. pneumophila in the lungs declined, whereas the burden of flagellin mutants increased. Accordingly, macrophages respond to cytosolic flagellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinflammatory cytokines that control L. pneumophila infection.<\/jats:p>","DOI":"10.1084\/jem.20051659","type":"journal-article","created":{"date-parts":[[2006,4,11]],"date-time":"2006-04-11T00:33:39Z","timestamp":1144715619000},"page":"1093-1104","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":407,"title":["Cytosolic recognition of flagellin by mouse macrophages restricts <i>Legionella pneumophila<\/i> infection"],"prefix":"10.1084","volume":"203","author":[{"given":"Ari B.","family":"Molofsky","sequence":"first","affiliation":[{"name":"1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109"}]},{"given":"Brenda G.","family":"Byrne","sequence":"additional","affiliation":[{"name":"1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109"}]},{"given":"Natalie N.","family":"Whitfield","sequence":"additional","affiliation":[{"name":"1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109"}]},{"given":"Cressida A.","family":"Madigan","sequence":"additional","affiliation":[{"name":"1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109"}]},{"given":"Etsu T.","family":"Fuse","sequence":"additional","affiliation":[{"name":"2Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Ohtaku, Tokyo 143-8540, Japan"}]},{"given":"Kazuhiro","family":"Tateda","sequence":"additional","affiliation":[{"name":"2Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Ohtaku, Tokyo 143-8540, Japan"}]},{"given":"Michele S.","family":"Swanson","sequence":"additional","affiliation":[{"name":"1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109"}]}],"member":"291","published-online":{"date-parts":[[2006,4,10]]},"reference":[{"key":"2023072513371666900_BIB1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/ni1112","volume":"5","year":"2004","journal-title":"Nat. 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