The Liver-Stage Plasmodium Infection Is a Critical Checkpoint for Development of Experimental Cerebral Malaria
Cerebral malaria is a life-threatening complication of malaria in humans, and the underlying pathogenic mechanisms are widely analyzed in a murine model of experimental cerebral malaria (ECM). Here, we show abrogation of ECM by hemocoel sporozoite-induced infection of a transgenic Plasmodium berghei...
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doaj-e92429c945c542ce9411d772d204182b2020-11-25T01:17:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02554470424The Liver-Stage Plasmodium Infection Is a Critical Checkpoint for Development of Experimental Cerebral MalariaYuko Sato0Yuko Sato1Stefanie Ries2Werner Stenzel3Simon Fillatreau4Simon Fillatreau5Simon Fillatreau6Simon Fillatreau7Kai Matuschewski8Kai Matuschewski9Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, GermanyDepartment of Microbiology and Immunology, Keio University School of Medicine, Tokyo, JapanImmune Regulation Research Group, Deutsches Rheuma-Forschungszentrum, Berlin, GermanyDepartment of Neuropathology, Charité - Universitätmedizin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, GermanyImmune Regulation Research Group, Deutsches Rheuma-Forschungszentrum, Berlin, GermanyDepartment of Immunology, Infectiology and Haematology (I2H), Institut Necker-Enfants Malades, INSERM U1151-CNRS UMR 8253, Paris, FranceFaculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, FranceAP-HP, Hôpital Necker Enfants Malades, Paris, FranceParasitology Unit, Max Planck Institute for Infection Biology, Berlin, GermanyDepartment of Molecular Parasitology, Institute of Biology, Humboldt University, Berlin, GermanyCerebral malaria is a life-threatening complication of malaria in humans, and the underlying pathogenic mechanisms are widely analyzed in a murine model of experimental cerebral malaria (ECM). Here, we show abrogation of ECM by hemocoel sporozoite-induced infection of a transgenic Plasmodium berghei line that overexpresses profilin, whereas these parasites remain fully virulent in transfusion-mediated blood infection. We, thus, demonstrate the importance of the clinically silent liver-stage infection for modulating the onset of ECM. Even though both parasites triggered comparable splenic immune cell expansion and accumulation of antigen-experienced CD8+ T cells in the brain, infection with transgenic sporozoites did not lead to cerebral vascular damages and suppressed the recruitment of overall lymphocyte populations. Strikingly, infection with the transgenic strain led to maintenance of CD115+Ly6C+ monocytes, which disappear in infected animals prone to ECM. An early induction of IL-10, IL-12p70, IL-6, and TNF at the time when parasites emerge from the liver might lead to a diminished induction of hepatic immunity. Collectively, our study reveals the essential role of early host interactions in the liver that may dampen the subsequent pro-inflammatory immune responses and influence the occurrence of ECM, highlighting a novel checkpoint in this fatal pathology.https://www.frontiersin.org/article/10.3389/fimmu.2019.02554/fullPlasmodiummalariacerebral malariaexperimental cerebral malarialiver-stagepre-erythrocytic stage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuko Sato Yuko Sato Stefanie Ries Werner Stenzel Simon Fillatreau Simon Fillatreau Simon Fillatreau Simon Fillatreau Kai Matuschewski Kai Matuschewski |
spellingShingle |
Yuko Sato Yuko Sato Stefanie Ries Werner Stenzel Simon Fillatreau Simon Fillatreau Simon Fillatreau Simon Fillatreau Kai Matuschewski Kai Matuschewski The Liver-Stage Plasmodium Infection Is a Critical Checkpoint for Development of Experimental Cerebral Malaria Frontiers in Immunology Plasmodium malaria cerebral malaria experimental cerebral malaria liver-stage pre-erythrocytic stage |
author_facet |
Yuko Sato Yuko Sato Stefanie Ries Werner Stenzel Simon Fillatreau Simon Fillatreau Simon Fillatreau Simon Fillatreau Kai Matuschewski Kai Matuschewski |
author_sort |
Yuko Sato |
title |
The Liver-Stage Plasmodium Infection Is a Critical Checkpoint for Development of Experimental Cerebral Malaria |
title_short |
The Liver-Stage Plasmodium Infection Is a Critical Checkpoint for Development of Experimental Cerebral Malaria |
title_full |
The Liver-Stage Plasmodium Infection Is a Critical Checkpoint for Development of Experimental Cerebral Malaria |
title_fullStr |
The Liver-Stage Plasmodium Infection Is a Critical Checkpoint for Development of Experimental Cerebral Malaria |
title_full_unstemmed |
The Liver-Stage Plasmodium Infection Is a Critical Checkpoint for Development of Experimental Cerebral Malaria |
title_sort |
liver-stage plasmodium infection is a critical checkpoint for development of experimental cerebral malaria |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-11-01 |
description |
Cerebral malaria is a life-threatening complication of malaria in humans, and the underlying pathogenic mechanisms are widely analyzed in a murine model of experimental cerebral malaria (ECM). Here, we show abrogation of ECM by hemocoel sporozoite-induced infection of a transgenic Plasmodium berghei line that overexpresses profilin, whereas these parasites remain fully virulent in transfusion-mediated blood infection. We, thus, demonstrate the importance of the clinically silent liver-stage infection for modulating the onset of ECM. Even though both parasites triggered comparable splenic immune cell expansion and accumulation of antigen-experienced CD8+ T cells in the brain, infection with transgenic sporozoites did not lead to cerebral vascular damages and suppressed the recruitment of overall lymphocyte populations. Strikingly, infection with the transgenic strain led to maintenance of CD115+Ly6C+ monocytes, which disappear in infected animals prone to ECM. An early induction of IL-10, IL-12p70, IL-6, and TNF at the time when parasites emerge from the liver might lead to a diminished induction of hepatic immunity. Collectively, our study reveals the essential role of early host interactions in the liver that may dampen the subsequent pro-inflammatory immune responses and influence the occurrence of ECM, highlighting a novel checkpoint in this fatal pathology. |
topic |
Plasmodium malaria cerebral malaria experimental cerebral malaria liver-stage pre-erythrocytic stage |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02554/full |
work_keys_str_mv |
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