{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T05:17:14Z","timestamp":1741411034708,"version":"3.38.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cerebral malaria is one of the most severe complications of malaria disease, attributed to a complicated series of immune reactions in the host. The syndrome is marked by inflammatory immune responses, margination of leukocytes, and parasitized erythrocytes in cerebral vessels leading to breakdown of the blood\u2013brain barrier. We show that chemical attenuation of the parasite at the very early, clinically silent liver stage suppresses parasite development, delays the time until parasites establish blood-stage infection, and provokes an altered host immune response, modifying immunopathogenesis and protecting from cerebral disease. The early response is proinflammatory and cell mediated, with increased T cell activation in the liver and spleen, and greater numbers of effector T cells, cytokine-secreting T cells, and proliferating, proinflammatory cytokine-producing T cells. Dendritic cell numbers, T cell activation, and infiltration of CD8+ T cells to the brain are decreased later in infection, possibly mediated by the anti-inflammatory cytokine IL-10. Strikingly, protection can be transferred to naive animals by adoptive transfer of lymphocytes from the spleen at very early times of infection. Our data suggest that a subpopulation belonging to CD8+ T cells as early as day 2 postinfection is responsible for protection. These data indicate that liver stage\u2013directed early immune responses can moderate the overall downstream host immune response and modulate severe malaria outcome.<\/jats:p>","DOI":"10.4049\/jimmunol.1400863","type":"journal-article","created":{"date-parts":[[2015,4,11]],"date-time":"2015-04-11T03:56:25Z","timestamp":1428724585000},"page":"4860-4870","source":"Crossref","is-referenced-by-count":18,"title":["Chemical Attenuation of <i>Plasmodium<\/i> in the Liver Modulates Severe Malaria Disease Progression"],"prefix":"10.1093","volume":"194","author":[{"given":"Matthew D","family":"Lewis","sequence":"first","affiliation":[{"name":"Centre for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital , D 69120 Heidelberg ,","place":["Germany"]},{"name":"German Centre for Infection Research , D 69120 Heidelberg ,","place":["Germany"]}]},{"given":"Jochen","family":"Behrends","sequence":"additional","affiliation":[{"name":"Core Facility Fluorescence Cytometry, Research Center Borstel , D 23845 Borstel ,","place":["Germany"]}]},{"given":"Cl\u00e1udia","family":"S\u00e1 e Cunha","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisbon ,","place":["Portugal"]}]},{"given":"Ant\u00f3nio M","family":"Mendes","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisbon ,","place":["Portugal"]}]},{"given":"Felix","family":"Lasitschka","sequence":"additional","affiliation":[{"name":"German Centre for Infection Research , D 69120 Heidelberg ,","place":["Germany"]},{"name":"Institute of Pathology, Heidelberg University Hospital , D 69120 Heidelberg ,","place":["Germany"]}]},{"given":"Julia M","family":"Sattler","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital , D 69120 Heidelberg ,","place":["Germany"]}]},{"given":"Kirsten","family":"Heiss","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital , D 69120 Heidelberg ,","place":["Germany"]},{"name":"MalVa GmbH , D 69121 Heidelberg ,","place":["Germany"]}]},{"given":"Taco W A","family":"Kooij","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre , 6500 HB Nijmegen ,","place":["the Netherlands"]},{"name":"Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre , 6500 HB Nijmegen ,","place":["the Netherlands"]}]},{"given":"Miguel","family":"Prud\u00eancio","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisbon ,","place":["Portugal"]}]},{"given":"Gerhard","family":"Bringmann","sequence":"additional","affiliation":[{"name":"Institute for Organic Chemistry, University of W\u00fcrzburg , 97074 W\u00fcrzburg ,","place":["Germany"]}]},{"given":"Friedrich","family":"Frischknecht","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital , D 69120 Heidelberg ,","place":["Germany"]}]},{"given":"Ann-Kristin","family":"Mueller","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases, Parasitology Unit, Heidelberg University Hospital , D 69120 Heidelberg ,","place":["Germany"]},{"name":"German Centre for Infection Research , D 69120 Heidelberg ,","place":["Germany"]}]}],"member":"286","published-online":{"date-parts":[[2015,5,15]]},"reference":[{"key":"2025030706225782900_r1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.pathol.2.010506.091913","article-title":"Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease","volume":"2","author":"Haldar","year":"2007","journal-title":"Annu. 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