{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:30:24Z","timestamp":1790937024476,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Legionella pneumophila (Lp), an important cause of morbidity and mortality from pneumonia, infects alveolar macrophages (AMs) and is recognized by several TLRs as well as Birc1e (NAIP5) and IL-1 converting enzyme-protease activating factor. We examined the role of TLR5 during the murine response to aerosolized Lp infection. At 4 h after infection, Tlr5\u2212\/\u2212 mice had lower numbers of polymorphonuclear neutrophils (PMNs) in their broncho-alveolar lavage fluid in comparison to wild-type (WT) mice. At 24 and 72 h, the PMN recruitment was similar. WT mice infected with a flagellin-deficient strain (LpFlaA\u2212) also showed an impaired early PMN response at 4 h compared with those infected with the WT strain. There was no consistent difference in bacterial counts at any of the time points when comparing the Tlr5\u2212\/\u2212 and WT mice. However, at 6 days after infection, the Tlr5\u2212\/\u2212 mice had increased leukocytic infiltrates in the alveolar and peribronchial interstitial spaces that were consistent with organizing pneumonia. We also examined the role of TLR5 during macrophage infection. In contrast to bone marrow-derived macrophages, AMs secreted TNF-\u03b1 after stimulation with purified flagellin. In addition, WT, but not Tlr5\u2212\/\u2212, AMs produced TNF-\u03b1 after stimulation with Lp. Live LpFlaA\u2212 did not induce TNF-\u03b1 secretion in AM. These results suggested that AMs recognize Lp flagellin and that a majority of the Lp-induced TNF-\u03b1 response is TLR5-mediated. Thus, TLR5 mediates recognition of Lp in AMs and performs a distinct role during the in vivo pulmonary immune response through regulation of early PMN recruitment and subsequent later development of pneumonia.<\/jats:p>","DOI":"10.4049\/jimmunol.179.10.6981","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:47:08Z","timestamp":1397864828000},"page":"6981-6987","source":"Crossref","is-referenced-by-count":99,"title":["Altered Inflammatory Responses in TLR5-Deficient Mice Infected with <i>Legionella pneumophila<\/i>"],"prefix":"10.1093","volume":"179","author":[{"given":"Thomas R","family":"Hawn","sequence":"first","affiliation":[{"name":"University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R","family":"Berrington","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Research Institute for Microbial Diseases, Osaka University , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Research Institute for Microbial Diseases, Osaka University , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Aderem","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology , Seattle, WA 98103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly D","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn J","family":"Skerrett","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,11,15]]},"reference":[{"key":"2025032800071872200_R1","first-page":"1991","volume-title":"Lancet","year":"2003"},{"key":"2025032800071872200_R2","first-page":"567","volume-title":"Annu. 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