{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T03:19:14Z","timestamp":1765423154774,"version":"3.41.2"},"reference-count":82,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"vor","delay-in-days":92,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1132975","1137285"],"award-info":[{"award-number":["1132975","1137285"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The sickle\u2010cell trait phenotype is associated with protection from malaria. Multiple molecular mechanisms have been proposed to explain this protection, but the role of the host immune system has been poorly investigated. We hypothesised that cellular immunity to malaria may develop differently in sickle\u2010cell trait children (HbAS) and children with normal haemoglobin (HbAA) repeatedly exposed to <jats:italic>Plasmodium falciparum<\/jats:italic> (<jats:italic>Pf<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Paired samples collected prior to the <jats:italic>Pf<\/jats:italic> transmission season and during the first malaria episode of the ensuing transmission season from HbAS and HbAA children were analysed by multiplex bead\u2010based assay and comprehensive multi\u2010dimensional flow cytometry profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cellular immune profiles were enriched in HbAS relative to HbAA children before the start of the <jats:italic>Pf<\/jats:italic> transmission season, with a distinct NK subset. These cells were identified as a novel subset of memory\u2010activated NK cells characterised by reduced expression of the ecto\u2010enzyme CD38 as well as co\u2010expression of high levels of HLA\u2010DR and CD45RO. The frequency of this NK subset before the transmission season was negatively correlated with parasite density quantified during the first malaria episode of the ensuing transmission season. Functional assessment revealed that these CD38<jats:sup>dim<\/jats:sup> CD45RO<jats:sup>+<\/jats:sup> HLA\u2010DR<jats:sup>+<\/jats:sup> NK cells represent a important source of IFN\u2010\u03b3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that this novel memory\u2010activated NK cell subset may contribute to an accelerated and enhanced IFN\u2010\u03b3\u2010mediated immune response and to control of parasite density in individuals with the sickle\u2010cell trait. This distinct cellular immune profile may contribute to predispose HbAS children to a relative protection from malaria.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1125","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T11:05:02Z","timestamp":1585825502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A novel population of memory\u2010activated natural killer cells associated with low parasitaemia in <i>Plasmodium falciparum<\/i>\u2010exposed sickle\u2010cell trait children"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4504-5635","authenticated-orcid":false,"given":"Claire","family":"Loiseau","sequence":"first","affiliation":[{"name":"Centre for Molecular Therapeutics Australian Institute of Tropical Health &amp; Medicine James Cook University Cairns QLD Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ogobara K","family":"Doumbo","sequence":"additional","affiliation":[{"name":"Mali International Center of Excellence in Research University of Sciences, Technique and Technology of Bamako Bamako Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boubacar","family":"Traore","sequence":"additional","affiliation":[{"name":"Mali International Center of Excellence in Research University of Sciences, Technique and Technology of Bamako Bamako Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie L","family":"Brady","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics Australian Institute of Tropical Health &amp; Medicine James Cook University Cairns QLD Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Proietti","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics Australian Institute of Tropical Health &amp; Medicine James Cook University Cairns QLD Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina P","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics Australian Institute of Tropical Health &amp; Medicine James Cook University Cairns QLD Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5629-0412","authenticated-orcid":false,"given":"Peter D","family":"Crompton","sequence":"additional","affiliation":[{"name":"Malaria Infection Biology and Immunity Section Laboratory of Immunogenetics National Institute of Allergy and Infectious Diseases National Institutes of Health Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7354-8817","authenticated-orcid":false,"given":"Denise L","family":"Doolan","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics Australian Institute of Tropical Health &amp; Medicine James Cook University Cairns QLD Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4857.290"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-020-3105-3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08273-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/352595a0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/430744"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.06.009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-241844"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.17-0343"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/592224"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1104"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.4.1994"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/274701a0"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(70)90700-2"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.360396"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-11-3820"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/280245a0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711401105"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1804388115"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1213775"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.06.007"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.03.049"},{"key":"e_1_2_8_23_1","first-page":"270","article-title":"A new look at the protection of hemoglobin AS and AC genotypes against Plasmodium falciparum infection: a census tract approach","volume":"28","author":"Ringelhann B","year":"1976","journal-title":"Am J Hum Genet"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-9877(87)90193-9"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020128"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/28.4.793"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000978"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.13.2.118"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/192733a0"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1979.11687244"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir638"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00025-08"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/00034989859366"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv054"},{"key":"e_1_2_8_35_1","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.4049\/jimmunol.143.6.2038","article-title":"Role of IFN\u2010\u0194 in lethal and nonlethal malaria in susceptible and resistant murine hosts","volume":"143","author":"Shear HL","year":"1989","journal-title":"J Immunol"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.3.1453"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.65.5.1593-1598.1997"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3024.1997.d01-227.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040587"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005118"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1086\/339408"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.29.9.1757-1760.1991"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1086\/314689"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.10.5396"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000106"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03464.x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502049"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.02.013"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36806"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181681"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005031"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005839"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201041180"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-05-2058"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303211"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110900108"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1009"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1086\/648596"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1086\/592971"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.2001.00838.x"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181134"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006702"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.03027.x"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.11.7466"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac5722"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/13.4.397"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.11.3864"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.1032"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150434"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100762"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00900.x"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02324"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130417"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-13-393"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1332"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07665"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2032"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3227"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501996"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2017.22"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.12.011"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323318111"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep31291"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcti2.1125","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1125","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.1125","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1125","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T05:37:22Z","timestamp":1693805842000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":82,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/cti2.1125"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1125","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"type":"print","value":"2050-0068"},{"type":"electronic","value":"2050-0068"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"2019-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1125"}}