{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:13:37Z","timestamp":1779243217295,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,5,19]],"date-time":"2014-05-19T00:00:00Z","timestamp":1400457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08-HL103756"],"award-info":[{"award-number":["K08-HL103756"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01-HD064827"],"award-info":[{"award-number":["U01-HD064827"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Louis V. Gerstner Scholars Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Although human red blood cell (<jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content>) units may be refrigerator stored for up to 42 days, transfusion of older <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content>s acutely delivers a large bolus of iron to mononuclear phagocytes. Similarly, iron dextran circulates in plasma for hours to days and is progressively cleared by mononuclear phagocytes, which return iron to plasma. Finally, malaria infection continuously delivers iron to macrophages by intra\u2010 and extravascular hemolysis. Studies suggest that iron administration increases infectious risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design and Methods<\/jats:title><jats:p>To assess the effects of increased iron availability on susceptibility to infection, we infected mice with model <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>ram\u2010negative intracellular or extracellular pathogens (<jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>almonella typhimurium<\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>scherichia coli<\/jats:italic>, respectively), accompanied by <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content> transfusion, iron dextran administration, or malarial coinfection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In our mouse models, transfusion of older <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content>s exacerbates infection with both <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>ram\u2010negative pathogens. Although iron dextran exacerbates <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> infection to a similar extent as transfusion of corresponding amounts of iron, higher iron doses are required to produce comparable effects with <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>.\u2009typhimurium<\/jats:italic>. Coinfection of mice with <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>lasmodium yoelii<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>.\u2009typhimurium<\/jats:italic> produces overwhelming <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>almonella<\/jats:italic> sepsis. Finally, treating mice with antibiotics abrogates the enhancing effect on <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli<\/jats:italic> infection of both older <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content> transfusion and iron dextran administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Transfusion of older <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content>s exacerbates <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>ram\u2010negative infection to a similar extent as malaria coinfection or iron dextran administration. Appropriate antibiotic therapy abrogates the effect of older <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content> transfusions on infection with <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>.\u2009coli.<\/jats:italic> Iron delivery to macrophages may be an underappreciated mechanism mediating, at least some, adverse effects of <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content> transfusions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.12712","type":"journal-article","created":{"date-parts":[[2014,5,20]],"date-time":"2014-05-20T03:00:57Z","timestamp":1400554857000},"page":"2842-2851","source":"Crossref","is-referenced-by-count":47,"title":["Transfusion of stored blood impairs host defenses against <scp>G<\/scp>ram\u2010negative pathogens in mice"],"prefix":"10.1111","volume":"54","author":[{"given":"Kevin","family":"Prestia","sequence":"first","affiliation":[{"name":"Institute of Comparative Medicine Columbia University Medical Center\u2013New York Presbyterian Hospital  New York New York"},{"name":"Department of Pathology and Cell Biology Columbia University Medical Center\u2013New York Presbyterian Hospital  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila","family":"Bandyopadhyay","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Medical Center\u2013New York Presbyterian Hospital  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Slate","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine Columbia University Medical Center\u2013New York Presbyterian Hospital  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard O.","family":"Francis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Medical Center\u2013New York Presbyterian Hospital  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin P.","family":"Francis","sequence":"additional","affiliation":[{"name":"PerkinElmer  Alameda California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Spitalnik","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Medical Center\u2013New York Presbyterian Hospital  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Fidock","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Columbia University Medical Center\u2013New York Presbyterian Hospital  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary M.","family":"Brittenham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Columbia University Medical Center\u2013New York Presbyterian Hospital  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eldad A.","family":"Hod","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Medical Center\u2013New York Presbyterian Hospital  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,5,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)67962-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1542\/peds.60.6.908","article-title":"Increased incidence of gram\u2010negative neonatal sepsis with intramuscula iron administration","volume":"60","author":"Barry DM","year":"1977","journal-title":"Pediatrics"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1224577"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1024\/0300-9831\/a000051"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f4822"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/011981-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002042.pub2"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200304000-00005"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.137.6.711"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1999.39070701.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3182086094"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318184aa11"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e3181a5a8f9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3181e76274"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2009.01134.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-245001"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/vox.12058"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-371849"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5053.1074"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1960.tb06216.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-4758(00)01774-9"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(99)90024-X"},{"key":"e_1_2_7_24_1","first-page":"186","article-title":"Concomitant bacteria in the blood of malaria patients in Owerri, southeastern Nigeria","volume":"8","author":"Ukaga CN","year":"2006","journal-title":"Tanzan Health Res Bull"},{"key":"e_1_2_7_25_1","first-page":"133","article-title":"Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications","volume":"45","author":"Uneke CJ","year":"2008","journal-title":"J Vector Borne Dis"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.24.11470"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00887-09"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1086\/511437"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(99)90282-1"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/155.6.1319"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/02724936.1993.11747625"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-4453(83)90863-0"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040275"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.2478\/s11536-008-0092-0"},{"key":"e_1_2_7_35_1","first-page":"351","article-title":"Salmonellosis in Lagos, Nigeria: incidence of Plasmodium falciparum\u2010associated co\u2010infection, patterns of antimicrobial resistance, and emergence of reduced susceptibility to fluoroquinolones","volume":"25","author":"Akinyemi KO","year":"2007","journal-title":"J Health Popul Nutr"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1754"},{"key":"e_1_2_7_37_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.4049\/jimmunol.91.1.65","article-title":"The influence of hemolysis or blood loss on susceptibility to infection","volume":"91","author":"Kaye D","year":"1963","journal-title":"J Immunol"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2009.02173.x"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(96)70254-8"},{"key":"e_1_2_7_40_1","first-page":"46","article-title":"Red blood cell hemolysis during processing. Transf","volume":"16","author":"Sowemimo\u2010Coker SO","year":"2002","journal-title":"Med Rev"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-011-9409-6"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.109.2.197"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2012.144"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2012-303353"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01529.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1097(90)90522-R"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001118"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-462945"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12131"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2004.11.010"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ftrf.12712","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.12712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T19:13:23Z","timestamp":1696187603000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.12712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,19]]},"references-count":49,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1111\/trf.12712"],"URL":"https:\/\/doi.org\/10.1111\/trf.12712","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"value":"0041-1132","type":"print"},{"value":"1537-2995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,19]]}}}