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The mechanisms limiting<jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>reinfections in humans living in regions of malaria endemicity have mainly been explored by studying the resistance induced by the blood stage of infection. However, epidemiologic studies have suggested that in high-transmission areas, preerythrocytic stages also activate host resistance to reinfection. This, along with the recent discovery that liver infections trigger a specific and effective type I interferon (IFN) response, prompted us to hypothesize that this pre-erythrocyte-stage-induced resistance is linked to liver innate immunity. Here, we combined experimental approaches and mathematical modeling to recapitulate field studies and understand the molecular basis behind such resistance. We present a newly established mouse reinfection model and demonstrate that rodent malaria liver-stage infection inhibits reinfection. This protection relies on the activation of innate immunity and involves the type I IFN response and the antimicrobial cytokine gamma IFN (IFN-\u03b3). Importantly, mathematical simulations indicate that the predictions based on our experimental murine reinfection model fit available epidemiological data. Overall, our study revealed that liver-stage-induced innate immunity may contribute to the preerythrocytic resistance observed in humans in regions of malaria hyperendemicity.<\/jats:p>","DOI":"10.1128\/iai.02796-14","type":"journal-article","created":{"date-parts":[[2015,1,13]],"date-time":"2015-01-13T05:18:40Z","timestamp":1421126320000},"page":"1172-1180","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Innate Immunity Induced by Plasmodium Liver Infection Inhibits Malaria Reinfections"],"prefix":"10.1128","volume":"83","author":[{"given":"Peter","family":"Liehl","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Patr\u00edcia","family":"Meireles","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"In\u00eas S.","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Mykola","family":"Pinkevych","sequence":"additional","affiliation":[{"name":"Centre for Vascular Research, UNSW Australia, Sydney, NSW, Australia"}]},{"given":"Fernanda","family":"Baptista","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-1041","authenticated-orcid":false,"given":"Maria M.","family":"Mota","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Miles P.","family":"Davenport","sequence":"additional","affiliation":[{"name":"Centre for Vascular Research, UNSW Australia, Sydney, NSW, Australia"}]},{"given":"Miguel","family":"Prud\u00eancio","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60034-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1529"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.12.007"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121130"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5501.141"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129720"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.2.010506.091913"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2009.01138.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2006.00808.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.f.205"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1311"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2368"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0049"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2000.62.266"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-8-161"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2006.75.2_suppl.0750011"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2012.04.006"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2012.03.011"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3424"},{"key":"e_1_3_3_21_2","first-page":"613","article-title":"Epidemiological basis of malaria control","volume":"15","author":"Macdonald G","year":"1956","unstructured":"Macdonald G. 1956. 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