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In this study, we pursued previous findings that Gr1<jats:sup>+<\/jats:sup>cells are required to selectively limit growth of \u0394<jats:italic>yopM Y. pestis<\/jats:italic>and that CD11b<jats:sup>+<\/jats:sup>cells other than polymorphonuclear leukocytes (PMNs) are selectively lost in spleens infected with parent<jats:italic>Y. pestis<\/jats:italic>. When PMNs were ablated from mice, \u0394<jats:italic>yopM Y. pestis<\/jats:italic>grew as well as the parent strain in liver but not in spleen, showing that these cells are critical for controlling growth of the mutant in liver but not spleen. In mice lacking expression of the chemokine receptor CCR2, wild-type growth was restored to \u0394<jats:italic>yopM Y. pestis<\/jats:italic>in both organs. In spleen, the Gr1<jats:sup>+<\/jats:sup>cells differentially recruited by parent and \u0394<jats:italic>yopM Y. pestis<\/jats:italic>infections were CCR2<jats:sup>+<\/jats:sup>Gr1<jats:sup>+<\/jats:sup>CD11b<jats:sup>+<\/jats:sup>CD11c<jats:sup>Lo-Int<\/jats:sup>MAC3<jats:sup>+<\/jats:sup>iNOS<jats:sup>+<\/jats:sup>(inducible nitric oxide synthase-positive) inflammatory dendritic cells (iDCs), and their recruitment to spleen from blood was blocked when YopM was present in the infecting strain. Consistent with influx of iDCs being affected by YopM in spleen, the growth defect of the \u0394<jats:italic>yopM<\/jats:italic>mutant was relieved by the parent<jats:italic>Y. pestis<\/jats:italic>strain in a coinfection assay in which the parent strain could affect the fate of the mutant in<jats:italic>trans<\/jats:italic>. In a mouse model of bubonic plague, CCR2 also was shown to be required for \u0394<jats:italic>yopM Y. pestis<\/jats:italic>to show wild-type growth in skin. The data imply that YopM's pathogenic effect indirectly undermines signaling through CCR2. We propose a model for how YopM exerts its different effects in liver and spleen.<\/jats:p>","DOI":"10.1128\/iai.00808-10","type":"journal-article","created":{"date-parts":[[2010,12,14]],"date-time":"2010-12-14T04:43:35Z","timestamp":1292301815000},"page":"674-687","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Distinct CCR2<sup>+<\/sup>Gr1<sup>+<\/sup>Cells Control Growth of the<i>Yersinia pestis<\/i>\u0394<i>yopM<\/i>Mutant in Liver and Spleen during Systemic Plague"],"prefix":"10.1128","volume":"79","author":[{"given":"Zhan","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette M.","family":"Uittenbogaard","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan M.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayakrishna","family":"Ambati","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan C.","family":"Straley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40536-0298"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408026101"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm950"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081385"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2005.00039.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119798"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0903442"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.4.821-835.2001"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0904554"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0407247"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2008.0027"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-007-0061-8"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00219-07"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00174-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.045146"},{"key":"e_1_3_3_16_2","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.4049\/jimmunol.157.6.2514","volume":"157","year":"1996","unstructured":"Gregory, S. 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