{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:19:33Z","timestamp":1787494773445,"version":"build-2736575974"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2001,4,1]],"date-time":"2001-04-01T00:00:00Z","timestamp":986083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2001,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The roles of CXC chemokine-mediated host responses were examined with an A\/J mouse model of\n                    <jats:italic>Legionella pneumophila<\/jats:italic>\n                    pneumonia. After intratracheal inoculation of 10\n                    <jats:sup>6<\/jats:sup>\n                    CFU of\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    , the bacterial numbers in the lungs increased 10-fold by day 2; this increase was accompanied by the massive accumulation of neutrophils. Reverse transcription-PCR data demonstrated the up-regulation of CXC chemokines, such as keratinocyte-derived chemokine, macrophage inflammatory protein 2 (MIP-2), and lipopolysaccharide-induced CXC chemokine (LIX). Consistent with these data, increased levels of KC, MIP-2, and LIX proteins were observed in the lungs and peaked at days 1, 2, and 2, respectively. Although the administration of anti-KC or anti\u2013MIP-2 antibody resulted in an approximately 20% decrease in neutrophil recruitment on day 2, no increase in mortality was observed. In contrast, the blockade of CXC chemokine receptor 2 (CXCR2), a receptor for CXC chemokines, including KC and MIP-2, strikingly enhanced mortality; this effect coincided with a 67% decrease in neutrophil recruitment. Interestingly, anti-CXCR2 antibody did not affect bacterial burden by day 2, even in the presence of a lethal challenge of bacteria. Moreover, a significant decrease in interleukin-12 (IL-12) levels, in contrast to the increases in KC, MIP-2, and LIX levels, was demonstrated for CXCR2-blocked mice. These data indicated that CXCR2-mediated neutrophil accumulation may play a crucial role in host defense against\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    pneumonia in mice. The increase in lethality without a change in early bacterial clearance suggested that neutrophils may exert their protective effect not through direct killing but through more immunomodulatory actions in\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    pneumonia. We speculate that a decrease in the levels of the protective cytokine IL-12 may explain, at least in part, the high mortality in the setting of reduced neutrophil recruitment.\n                  <\/jats:p>","DOI":"10.1128\/iai.69.4.2017-2024.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:03:59Z","timestamp":1027749839000},"page":"2017-2024","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":123,"title":["Chemokine-Dependent Neutrophil Recruitment in a Murine Model of\n                    <i>Legionella<\/i>\n                    Pneumonia: Potential Role of Neutrophils as Immunoregulatory Cells"],"prefix":"10.1128","volume":"69","author":[{"given":"Kazuhiro","family":"Tateda","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0360,1 and"},{"name":"<!--label omitted: 2-->Department of Microbiology, Toho University School of Medicine, Tokyo 143-0015, Japan2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Moore","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0360,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Newstead","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0360,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan C.","family":"Tsai","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0360,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianying","family":"Zeng","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0360,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C.","family":"Deng","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0360,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Chen","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0360,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Reddy","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0360,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Microbiology, Toho University School of Medicine, Tokyo 143-0015, Japan2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore J.","family":"Standiford","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0360,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"7216","DOI":"10.4049\/jimmunol.151.12.7216","article-title":"Recruitment of inflammatory cells to the pleural space. Chemotactic cytokines, IL-8, and monocyte chemotactic peptide-1 in human pleural fluids","volume":"151","author":"Antony V. B.","year":"1993","unstructured":"Antony V. B. Godbey S. W. Kunkel S. L. Hott J. W. Hartman D. L. Burdick M. D. Strieter R. M. Recruitment of inflammatory cells to the pleural space. Chemotactic cytokines, IL-8, and monocyte chemotactic peptide-1 in human pleural fluids.J. Immunol.151199372167223","journal-title":"J. Immunol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.45.6.538"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"7369","DOI":"10.4049\/jimmunol.162.12.7369","article-title":"Human polymorphonuclear leukocytes produce IL-12, TNF-alpha, and the chemokines macrophage-inflammatory protein-1 alpha and -1 beta in response to Toxoplasma gondii antigens","volume":"162","author":"Bliss S. K.","year":"1999","unstructured":"Bliss S. K. Marshall A. J. Zhang Y. Denkers E. Y. Human polymorphonuclear leukocytes produce IL-12, TNF-alpha, and the chemokines macrophage-inflammatory protein-1 alpha and -1 beta in response to Toxoplasma gondii antigens.J. Immunol.162199973697375","journal-title":"J. Immunol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.4049\/jimmunol.163.4.2081","article-title":"Murine neutrophil stimulation by Toxoplasma gondii antigen drives high level production of IFN-gamma-independent IL-12","volume":"163","author":"Bliss S. K.","year":"1999","unstructured":"Bliss S. K. Zhang Y. Denkers E. Y. Murine neutrophil stimulation by Toxoplasma gondii antigen drives high level production of IFN-gamma-independent IL-12.J. Immunol.163199920812088","journal-title":"J. Immunol."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)43882-3"},{"key":"e_1_3_2_7_2","first-page":"1537","article-title":"Replicative Legionella pneumophila lung infection in intratracheally inoculated A\/J mice. A murine model of human Legionnaires' disease","volume":"145","author":"Brieland J.","year":"1994","unstructured":"Brieland J. Freeman P. Kunkel R. Chrisp C. Hurley M. Fantone J. Engleberg N. C. Replicative Legionella pneumophila lung infection in intratracheally inoculated A\/J mice. A murine model of human Legionnaires' disease.Am. J. Pathol.145199415371546","journal-title":"Am. J. Pathol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.9.3253-3258.1995"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.1.65-69.1998"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.7.3029-3034.1998"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.149.3.8118629"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250102"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.1.259"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.156.5.97-04039"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.8.3197-3205.1994"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4049\/jimmunol.148.2.457","article-title":"Cytokine-stimulated human mesothelial cells produce chemotactic activity for neutrophils including NAP-1\/IL-8","volume":"148","author":"Goodman R. B.","year":"1992","unstructured":"Goodman R. B. Wood R. G. Martin T. R. Hanson-Painton O. Kinasewitz G. T. Cytokine-stimulated human mesothelial cells produce chemotactic activity for neutrophils including NAP-1\/IL-8.J. Immunol.1481992457465","journal-title":"J. Immunol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"722","DOI":"10.4049\/jimmunol.155.2.722","article-title":"Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia","volume":"155","author":"Greenberger M. J.","year":"1995","unstructured":"Greenberger M. J. Strieter R. M. Kunkel S. L. Danforth J. M. Goodman R. E. Standiford T. J. Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia.J. Immunol.1551995722729","journal-title":"J. Immunol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90278-X"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)46662-2"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.153.2.386"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109874"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.4049\/jimmunol.138.11.3891","article-title":"The effect of LPS on expression of the early \u201ccompetence\u201d genes JE and KC in murine peritoneal macrophages","volume":"138","author":"Introna M.","year":"1987","unstructured":"Introna M. Bast R. C. Jr. Tannenbaum C. S. Hamilton T. A. Adams D. O. The effect of LPS on expression of the early \u201ccompetence\u201d genes JE and KC in murine peritoneal macrophages.J. Immunol.138198738913896","journal-title":"J. Immunol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.7.3164-3169.1998"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.4049\/jimmunol.155.4.2158","article-title":"Chemokine binding and activities mediated by the mouse IL-8 receptor","volume":"155","author":"Lee J.","year":"1995","unstructured":"Lee J. Cacalano G. Camerato T. Toy K. Moore M. W. Wood W. I. Chemokine binding and activities mediated by the mouse IL-8 receptor.J. Immunol.155199521582164","journal-title":"J. Immunol."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41997-7"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1994.00420210049006"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.4049\/jimmunol.163.5.2829","article-title":"Inhibition of murine neutrophil recruitment in vivo by CXC chemokine receptor antagonists","volume":"163","author":"McColl S. R.","year":"1999","unstructured":"McColl S. R. Clark-Lewis I. Inhibition of murine neutrophil recruitment in vivo by CXC chemokine receptor antagonists.J. Immunol.163199928292835","journal-title":"J. Immunol."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197712012972202"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"6086","DOI":"10.4049\/jimmunol.163.11.6086","article-title":"CXC chemokine receptor-2 ligands are necessary components of neutrophil-mediated host defense in invasive pulmonary aspergillosis","volume":"163","author":"Mehrad B.","year":"1999","unstructured":"Mehrad B. Strieter R. M. Moore T. A. Tsai W. C. Lira S. A. Standiford T. J. CXC chemokine receptor-2 ligands are necessary components of neutrophil-mediated host defense in invasive pulmonary aspergillosis.J. Immunol.163199960866094","journal-title":"J. Immunol."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111493"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1086\/516258"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.577-583.2000"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/clim.1999.4709"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/10.5.1018"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.3.909"},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"5349","DOI":"10.4049\/jimmunol.158.11.5349","article-title":"Neutrophil production of IL-12 and IL-10 in candidiasis and efficacy of IL-12 therapy in neutropenic mice","volume":"158","author":"Romani L.","year":"1997","unstructured":"Romani L. Mencacci A. Cenci E. Spaccapelo R. Del Sero G. Nicoletti I. Trinchieri G. Bistoni F. Puccetti P. Neutrophil production of IL-12 and IL-10 in candidiasis and efficacy of IL-12 therapy in neutropenic mice.J. Immunol.158199753495356","journal-title":"J. Immunol."},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"5490","DOI":"10.4049\/jimmunol.162.9.5490","article-title":"Lungkine, a novel CXC chemokine, specifically expressed by lung bronchoepithelial cells","volume":"162","author":"Rossi D. L.","year":"1999","unstructured":"Rossi D. L. Hurst S. D. Xu Y. Wang W. Menon S. Coffman R. L. Zlotnik A. Lungkine, a novel CXC chemokine, specifically expressed by lung bronchoepithelial cells.J. Immunol.162199954905497","journal-title":"J. Immunol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.64.4.494"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.28.16756"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1086\/515040"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.001343"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.4289-4296.2000"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/148.3.510"},{"key":"e_1_3_2_44_2","first-page":"344","article-title":"The pathology of Legionnaires' disease. Fourteen fatal cases from the 1977 outbreak in Vermont","volume":"102","author":"Winn W. C.","year":"1978","unstructured":"Winn W. C. Jr. Glavin F. L. Perl D. P. Keller J. L. Andres T. L. Brown T. M. Coffin C. M. Sensecqua J. E. Roman L. N. Craighead J. E. The pathology of Legionnaires' disease. Fourteen fatal cases from the 1977 outbreak in Vermont.Arch. Pathol. Lab. Med.1021978344350","journal-title":"Arch. Pathol. Lab. Med."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(81)80021-4"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.2.570"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.2.612"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.69.4.2017-2024.2001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.69.4.2017-2024.2001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T11:46:00Z","timestamp":1682250360000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.69.4.2017-2024.2001"}},"subtitle":[],"editor":[{"given":"E. I.","family":"Tuomanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2001,4]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,4]]}},"alternative-id":["10.1128\/IAI.69.4.2017-2024.2001"],"URL":"https:\/\/doi.org\/10.1128\/iai.69.4.2017-2024.2001","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,4]]},"assertion":[{"value":"2000-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-01-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}