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In patients with a variety of infectious and noninfectious inflammatory disorders, histiocytes can engulf nonapoptotic leukocytes and nonsenescent erythrocytes and thus become hemophagocytes. We report here the identification and characterization of splenic hemophagocytes in a natural model of murine typhoid fever. The development of a flow-cytometric method allowed us to identify hemophagocytes based on their greater than 6N (termed 6N+) DNA content. Characterization of the 6N+ population from infected mice showed that these cells consist primarily of macrophages rather than dendritic cells and contain T lymphocytes, consistent with hemophagocytosis. Most 6N+ macrophages from<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella enterica<\/jats:named-content>serovar Typhimurium-infected mice contain intact DNA, consistent with hemophagocytosis. In contrast, most 6N+ macrophages from control mice or mice infected with a different bacterial pathogen,<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Yersinia pseudotuberculosis<\/jats:named-content>, contain damaged DNA. Finally, 6N+ splenic macrophages from<jats:italic>S<\/jats:italic>. Typhimurium-infected mice express markers consistent with an anti-inflammatory M2 activation state rather than a classical M1 activation state. We conclude that macrophages are the predominant splenic hemophagocyte in this disease model but not in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Y. pseudotuberculosis<\/jats:named-content>-infected mice. The anti-inflammatory phenotype of hemophagocytic macrophages suggests that these cells contribute to the shift from acute to chronic infection.<\/jats:p>","DOI":"10.1128\/iai.00656-12","type":"journal-article","created":{"date-parts":[[2012,8,7]],"date-time":"2012-08-07T02:20:02Z","timestamp":1344306002000},"page":"3642-3649","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Hemophagocytic Macrophages in Murine Typhoid Fever Have an Anti-Inflammatory Phenotype"],"prefix":"10.1128","volume":"80","author":[{"given":"Melissa W.","family":"McCoy","sequence":"first","affiliation":[{"name":"Department of Molecular Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Moreland","sequence":"additional","affiliation":[{"name":"Department of Molecular Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrella S.","family":"Detweiler","sequence":"additional","affiliation":[{"name":"Department of Molecular Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.10.7147"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060905"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-421-0_28"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000573"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.4.1187"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009441"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.16.4601-4611.2002"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.4049\/jimmunol.156.8.2894","article-title":"Genetically resistant (Ityr) and susceptible (Itys) congenic mouse strains show similar cytokine responses following infection with Salmonella dublin","volume":"156","author":"Eckmann L","year":"1996","unstructured":"EckmannLFiererJKagnoffMF. 1996. 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