{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:57:45Z","timestamp":1780066665044,"version":"3.54.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T00:00:00Z","timestamp":1418083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,12,31]],"date-time":"2014-12-31T00:00:00Z","timestamp":1419984000000},"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":["mBio"],"published-print":{"date-parts":[[2014,12,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Hemophagocytes are cells of the monocyte lineage that have engulfed erythrocytes and leukocytes. Hemophagocytes frequently accumulate in patients with severe acute bacterial infections, such as those caused by<jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content>,<jats:named-content content-type=\"genus-species\">Brucella abortus<\/jats:named-content>, and<jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>. The relationship between hemophagocytosis and infection is not well understood. In the murine liver,<jats:named-content content-type=\"genus-species\">S. enterica<\/jats:named-content>serovar Typhimurium resides within hemophagocytic macrophages containing leukocytes. Here we show that<jats:italic>S<\/jats:italic>.\u00a0Typhimurium also resides within hemophagocytes containing erythrocytes. In cell culture,<jats:italic>S<\/jats:italic>.\u00a0Typhimurium benefits from residence within hemophagocytes by accessing iron, but why macrophages hemophagocytose is unknown. We show that treatment of macrophages with a cocktail of the proinflammatory cytokine interferon gamma (IFN-\u03b3) and lipopolysaccharide (LPS) stimulates engulfment of nonsenescent erythrocytes. Exposure of resting or IFN-\u03b3-treated macrophages to live, but not to heat-killed,<jats:italic>S<\/jats:italic>.\u00a0Typhimurium cells also stimulates erythrocyte engulfment. Single-cell analyses show that<jats:italic>S<\/jats:italic>.\u00a0Typhimurium-infected macrophages are more likely to erythrophagocytose and that infected macrophages engulf more erythrocytes than uninfected macrophages within the same culture well. In addition, macrophages containing erythrocytes harbor more bacteria. However,<jats:italic>S<\/jats:italic>.\u00a0Typhimurium does not promote macrophage engulfment of polystyrene beads, suggesting a role for a ligand on the target cell. Finally, neither of the two<jats:italic>S<\/jats:italic>.\u00a0Typhimurium type 3 secretion systems, T3SS1 or T3SS2, is fully required for hemophagocytosis. These results indicate that infection of macrophages with live<jats:italic>S.\u00a0Typhimurium<\/jats:italic>cells stimulates hemophagocytosis.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Macrophages are white blood cells (leukocytes) that engulf and destroy pathogens. Hemophagocytes, a subset of macrophages, are characteristic of severe acute infection in patients with, for instance, typhoid fever, brucellosis, tuberculosis, and leishmaniasis. Each of these diseases has the potential to become chronic. Hemophagocytes (blood-eating cells) engulf and degrade red and white blood cells for unknown reasons. The bacterial pathogen<jats:italic>Salmonella<\/jats:italic>acquires the essential nutrient iron from murine hemophagocytes. We report that<jats:italic>Salmonella<\/jats:italic>stimulates macrophages to engulf blood cells, indicating that cells of this bacterium actively promote the formation of a specialized cellular niche in which they can acquire nutrients, evade killing by the host immune system, and potentially transition to chronic infection.<\/jats:p>","DOI":"10.1128\/mbio.02211-14","type":"journal-article","created":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T02:33:25Z","timestamp":1418178805000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Salmonella enterica Infection Stimulates Macrophages to Hemophagocytose"],"prefix":"10.1128","volume":"5","author":[{"given":"M. Carolina","family":"Pilonieta","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":"Christopher N.","family":"English","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_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1788"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01369-10"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030193"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0606.000608"},{"key":"e_1_3_2_6_2","volume-title":"The principles and practice of medicine","author":"Osler SW","year":"1892","unstructured":"OslerSW . 1892. The principles and practice of medicine. D. Appleton and Company, New York, NY."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.1994.9.1.57"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00656-12"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009441"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-198605000-00018"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-012-0728-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2257.2005.00717.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1111\/mmi.12739","article-title":"Salmonella acquires ferrous iron from haemophagocytic macrophages","volume":"93","author":"Nagy TA","year":"2014","unstructured":"NagyTA MorelandSM DetweilerCS . 2014. Salmonella acquires ferrous iron from haemophagocytic macrophages. Mol. Microbiol. 93:1314\u20131326.","journal-title":"Mol. Microbiol."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1994.tb04905.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20102538"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43157"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-255174"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-08-521625"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.06.019"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.13.5976"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.3.6.611"},{"key":"e_1_3_2_22_2","volume-title":"The principles and practice of medicine","author":"Osler W","year":"1912","unstructured":"OslerW McCraeT . 1912. The principles and practice of medicine, 8th ed. D. Appleton and Company, New York, NY.","edition":"8"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2460\/ajvr.1984.45.01.59","article-title":"Aromatic-dependent Salmonella typhimurium as modified live vaccines for calves","volume":"45","author":"Smith BP","year":"1984","unstructured":"SmithBP Reina-GuerraM HoisethSK StockerBA HabashaF JohnsonE MerrittF . 1984. Aromatic-dependent Salmonella typhimurium as modified live vaccines for calves. Am. J. Vet. Res. 45:59\u201366.","journal-title":"Am. J. Vet. Res."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.01-05-0273"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00887-09"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.8.2923-2929.1996"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.5.2225-2232.1999"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1107781"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0602325"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.227"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00292-10"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00125"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.02.001"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.13.4338-4349.1992"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.9.5050-5055.2000"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7618105"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913087107"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01701.x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031319"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.4.569"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2003.00296.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01368.x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.4049\/jimmunol.143.4.1223","article-title":"Endotoxin-macrophage interaction: post-translational regulation of tumor necrosis factor expression","volume":"143","author":"Zuckerman SH","year":"1989","unstructured":"ZuckermanSH EvansGF SnyderYM RoederWD . 1989. Endotoxin-macrophage interaction: post-translational regulation of tumor necrosis factor expression. J. Immunol. 143:1223\u20131227.","journal-title":"J. Immunol."},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1177\/0300985813478213"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020201"},{"key":"e_1_3_2_46_2","first-page":"853","article-title":"Endogenous cachectin\/tumour necrosis factor-alpha production contributes to experimental cancer-associated cachexia","volume":"8","author":"Moldawer LL","year":"1989","unstructured":"MoldawerLL SherryB LowrySF CeramiA . 1989. Endogenous cachectin\/tumour necrosis factor-alpha production contributes to experimental cancer-associated cachexia. Cancer Surv. 8:853\u2013859.","journal-title":"Cancer Surv."},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-315218"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.260.1"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.37958"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.07.010"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000142184.49976.0c"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00688-09"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01381.x"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.11.4304"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.03.007"},{"key":"e_1_3_2_56_2","volume-title":"Physiology of the bacterial cell: a molecular approach","author":"Neidhardt FC","year":"1990","unstructured":"NeidhardtFC IngrahamJL SchaechterM . 1990. Physiology of the bacterial cell: a molecular approach. Sinauer Associates, Sunderland, MA."},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1979.tb12861.x"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(19970615)30:3<124::AID-CYTO3>3.0.CO;2-L"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02211-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02211-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:15:15Z","timestamp":1747181715000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.02211-14"}},"subtitle":[],"editor":[{"given":"Arturo","family":"Zychlinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,12,31]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,12,31]]}},"alternative-id":["10.1128\/mBio.02211-14"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02211-14","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,31]]},"assertion":[{"value":"2014-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-11-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02211-14"}}