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However, by introducing bacterial products into the host cytosol,<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>also activates cytosolic immunosurveillance pathways, thereby triggering robust proinflammatory responses that mediate the control of infection. Thus, the pulmonary cell types that<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>infects not only may act as an intracellular niche that facilitates its pathogenesis but also may contribute to the immune response against<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>. The identity of these host cells remains poorly understood. Here, we developed a strain of<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>producing a fusion protein consisting of \u03b2-lactamase fused to the T4SS-translocated effector RalF, which allowed us to track cells injected by the T4SS. Our data reveal that alveolar macrophages and neutrophils both are the primary recipients of T4SS-translocated effectors and harbor viable<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>during pulmonary infection of mice. Moreover, both alveolar macrophages and neutrophils from infected mice produced tumor necrosis factor and interleukin-1\u03b1 in response to T4SS-sufficient, but not T4SS-deficient,<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>. Collectively, our data suggest that alveolar macrophages and neutrophils are both an intracellular reservoir for<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>and a source of proinflammatory cytokines that contribute to the host immune response against<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>during pulmonary infection.<\/jats:p>","DOI":"10.1128\/iai.01891-14","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T03:38:42Z","timestamp":1407209922000},"page":"4325-4336","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":74,"title":["Alveolar Macrophages and Neutrophils Are the Primary Reservoirs for Legionella pneumophila and Mediate Cytosolic Surveillance of Type IV Secretion"],"prefix":"10.1128","volume":"82","author":[{"given":"Alan M.","family":"Copenhaver","sequence":"first","affiliation":[{"name":"Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cierra N.","family":"Casson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hieu T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Fung","sequence":"additional","affiliation":[{"name":"Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M.","family":"Duda","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig R.","family":"Roy","sequence":"additional","affiliation":[{"name":"Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunny","family":"Shin","sequence":"additional","affiliation":[{"name":"Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(96)10041-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197712012972201"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197712012972202"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70713-3"},{"key":"e_1_3_3_6_2","first-page":"407","article-title":"Factors influencing the case-fatality rate of Legionnaires' disease","volume":"13","author":"Dom\u00ednguez A","year":"2009","unstructured":"Dom\u00ednguezA AlvarezJ Sabri\u00e0M CarmonaG TornerN OviedoM CaylaJ MinguellS BarrabeigI SalaM GodoyP CampsN. 2009. 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