{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T17:22:37Z","timestamp":1774545757405,"version":"3.50.1"},"reference-count":72,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"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":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Eukaryotic high-mobility-group-box (HMGB) proteins are nuclear factors involved in chromatin remodeling and transcription regulation. When released into the extracellular milieu, HMGB1 acts as a proinflammatory cytokine that plays a central role in the pathogenesis of several immune-mediated inflammatory diseases. We found that the<jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>genome encodes two genuine HMGB factors,<jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>HMGB1 and HMGB2, that encompass, like their human counterparts, a proinflammatory domain. Given that these proteins are released from parasitized red blood cells, we then hypothesized that<jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>HMGB might contribute to the pathogenesis of experimental cerebral malaria (ECM), a lethal neuroinflammatory syndrome that develops in C57BL\/6 (susceptible) mice infected with<jats:named-content content-type=\"genus-species\">Plasmodium berghei<\/jats:named-content>ANKA and that in many aspects resembles human cerebral malaria elicited by<jats:named-content content-type=\"genus-species\">P. falciparum<\/jats:named-content>infection. The pathogenesis of experimental cerebral malaria was suppressed in C57BL\/6 mice infected with<jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>ANKA lacking the<jats:italic>hmgb2<\/jats:italic>gene (\u0394<jats:italic>hmgb2<\/jats:italic>ANKA), an effect associated with a reduction of histological brain lesions and with lower expression levels of several proinflammatory genes. The incidence of ECM in<jats:italic>pbhmgb2<\/jats:italic>-deficient mice was restored by the administration of recombinant<jats:italic>Pb<\/jats:italic>HMGB2. Protection from experimental cerebral malaria in \u0394<jats:italic>hmgb2<\/jats:italic>ANKA-infected mice was associated with reduced sequestration in the brain of CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells, including CD8<jats:sup>+<\/jats:sup>granzyme B<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>IFN-\u03b3<jats:sup>+<\/jats:sup>cells, and, to some extent, neutrophils. This was consistent with a reduced parasite sequestration in the brain, lungs, and spleen, though to a lesser extent than in wild-type<jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>ANKA-infected mice. In summary,<jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>HMGB2 acts as an alarmin that contributes to the pathogenesis of cerebral malaria.<\/jats:p>","DOI":"10.1128\/iai.03129-14","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T01:51:54Z","timestamp":1430185914000},"page":"2771-2784","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Disruption of Parasite<i>hmgb2<\/i>Gene Attenuates Plasmodium berghei ANKA Pathogenicity"],"prefix":"10.1128","volume":"83","author":[{"given":"Sylvie","family":"Briquet","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9s, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France"},{"name":"INSERM, U1135, CIMI-Paris, Paris, France"},{"name":"CNRS, ERL 8255, CIMI-Paris, Paris, France"}]},{"given":"Nadou","family":"Lawson-Hogban","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France"},{"name":"INSERM, U1135, CIMI-Paris, Paris, France"},{"name":"CNRS, ERL 8255, CIMI-Paris, Paris, France"}]},{"given":"Bertrand","family":"Boisson","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie et G\u00e9n\u00e9tique du Paludisme, Institut Pasteur, Paris, France"}]},{"given":"Miguel P.","family":"Soares","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal"}]},{"given":"Roger","family":"P\u00e9ronet","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie des Interactions H\u00f4tes Parasites, Institut Pasteur, Paris, France"},{"name":"Centre National Scientifique, Unit\u00e9 de Recherche Associ\u00e9e 2581, Paris, France"}]},{"given":"Leanna","family":"Smith","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie des Interactions H\u00f4tes Parasites, Institut Pasteur, Paris, France"},{"name":"Centre National Scientifique, Unit\u00e9 de Recherche Associ\u00e9e 2581, Paris, France"}]},{"given":"Robert","family":"M\u00e9nard","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie et G\u00e9n\u00e9tique du Paludisme, Institut Pasteur, Paris, France"}]},{"given":"Michel","family":"Huerre","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche et Expertises en Histotechnologie et Pathologie, Institut Pasteur, Paris, France"},{"name":"Centre National Scientifique, Unit\u00e9 de Recherche Associ\u00e9e 2581, Paris, France"}]},{"given":"Salah","family":"M\u00e9cheri","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie des Interactions H\u00f4tes Parasites, Institut Pasteur, Paris, France"},{"name":"Centre National Scientifique, Unit\u00e9 de Recherche Associ\u00e9e 2581, Paris, France"}]},{"given":"Catherine","family":"Vaquero","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9s, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France"},{"name":"INSERM, U1135, CIMI-Paris, Paris, France"},{"name":"CNRS, ERL 8255, CIMI-Paris, Paris, France"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"World malaria report","author":"WHO","year":"2014","unstructured":"WHO. 2014. World malaria report. WHO, Geneva, Switzerland."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2006.02.016"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2009.23"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.77.6.suppl.99"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph2005010123"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00229-1"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/315078"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1989.tb00552.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0607-667"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1586"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0368-5"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120455109"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-180"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090504"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep00039"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(99)80513-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/512083"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2010.03.006"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2004.01366.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2006.02.004"},{"key":"e_1_3_3_22_2","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.137.7.2348","article-title":"L3T4+ T lymphocytes play a major role in the pathogenesis of murine cerebral malaria","volume":"137","author":"Grau GE","year":"1986","unstructured":"Grau GE, Piguet PF, Engers HD, Louis JA, Vassalli P, Lambert PH. 1986. L3T4+ T lymphocytes play a major role in the pathogenesis of murine cerebral malaria. J Immunol 137:2348\u20132354.","journal-title":"J Immunol"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6369"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003955"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000944"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200006)30:6<1646::AID-IMMU1646>3.0.CO;2-0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018720"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.4.810-820.2001"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.06008-11"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2005.08.007"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2009.09.008"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.164.10.2106117"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00858"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.43.25752"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.16.4337"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200424916"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365540310016286"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000155991.88802.4D"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)02658-6"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.2119\/2006-00010.Yang"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.6.2950"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000259534.68873.2A"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03402105"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.35391"},{"key":"e_1_3_3_45_2","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1189\/jlb.72.6.1084","article-title":"HMGB1 as a DNA-binding cytokine","volume":"72","author":"Andersson U","year":"2002","unstructured":"Andersson U, Erlandsson-Harris H, Yang H, Tracey KJ. 2002. HMGB1 as a DNA-binding cytokine. J Leukoc Biol 72:1084\u20131091.","journal-title":"J Leukoc Biol"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2004.06.008"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-105"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.09.006"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-34"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.5.4.672-682.2006"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parint.2007.11.005"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2005.09.027"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1997.0507"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.53"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.248"},{"key":"e_1_3_3_56_2","volume-title":"The rat brain in stereotaxic coordinates","author":"Paxinos G","year":"1998","unstructured":"Paxinos G, Watson C. 1998. The rat brain in stereotaxic coordinates, 4th ed. Academic Press, San Diego, CA.","edition":"4"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.03.011"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.4.1144-1149.1994"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182009991715"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1867"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01441.x"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801637200"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/10338"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.8.1265"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1086\/498579"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1994.50.512"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1998.58.240"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.00290.x"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3156.1997.d01-355.x"},{"key":"e_1_3_3_70_2","first-page":"163","article-title":"HMGB1 and its physiological and pathological roles","volume":"113","author":"Naglova H","year":"2012","unstructured":"Naglova H, Bucova M. 2012. HMGB1 and its physiological and pathological roles. Bratisl Lek Listy 113:163\u2013171.","journal-title":"Bratisl Lek Listy"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2432"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2008.0184"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903419106"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.03129-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.03129-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T21:02:35Z","timestamp":1691614955000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.03129-14"}},"subtitle":[],"editor":[{"given":"J. H.","family":"Adams","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2015,7]]},"references-count":72,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.1128\/IAI.03129-14"],"URL":"https:\/\/doi.org\/10.1128\/iai.03129-14","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7]]},"assertion":[{"value":"2015-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}