gms | German Medical Science

12th Malaria Meeting

Malaria Group / Section Antiparasitic Chemotherapy of the Paul-Ehrlich-Society (PEG e. V.) in cooperation with the German Society for Tropical Medicine and International Health (DTG e. V.) and the German Society for Parasitology (DGP e. V.)

14.11. - 15.11.2014, Bonn

AAV8-mediated in vivo overexpression of miR-155 enhances the protective capacity of genetically-attenuated malarial parasites

Meeting Abstract

  • Franziska Hentzschel - Centre for Infectious Diseases, Parasitology, Heidelberg University Medical School, Heidelberg, Germany; Centre for Infectious Diseases, Virology, Heidelberg University Medical School, Heidelberg, Germany
  • Christiane Hammerschmidt-Kamper - Centre for Infectious Diseases, Parasitology, Heidelberg University Medical School, Heidelberg, Germany
  • Kathleen Börner - Centre for Infectious Diseases, Virology, Heidelberg University Medical School, Heidelberg, Germany
  • Kirsten Heiss - Centre for Infectious Diseases, Parasitology, Heidelberg University Medical School, Heidelberg, Germany
  • Bettina Knapp - ViroQuant Research Group Modeling, BioQuant, University of Heidelberg, Heidelberg, Germany; Cluster of Excellence CellNetworks, Heidelberg, Germany; Medical Faculty Carl Gustav Carus, Institute for Medical Informatics and Biometry, Dresden University of Technology, Dresden, Germany; Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany
  • Julia M. Sattler - Centre for Infectious Diseases, Parasitology, Heidelberg University Medical School, Heidelberg, Germany
  • Lars Kaderali - ViroQuant Research Group Modeling, BioQuant, University of Heidelberg, Heidelberg, Germany; Cluster of Excellence CellNetworks, Heidelberg, Germany; Medical Faculty Carl Gustav Carus, Institute for Medical Informatics and Biometry, Dresden University of Technology, Dresden, Germany
  • Mirco Castoldi - University Hospital Düsseldorf, Gastroenterology, Hepatology and Infectious Diseases,Düsseldorf, Germany
  • Julia G. Bindman - Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, USA
  • Yann Malato - Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, USA
  • Holger Willenbring - Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, USA; Liver Center, University of California San Francisco, San Francisco, USA
  • Ann-Kristin Mueller - Centre for Infectious Diseases, Parasitology, Heidelberg University Medical School, Heidelberg, Germany
  • Dirk Grimm - Centre for Infectious Diseases, Virology, Heidelberg University Medical School, Heidelberg, Germany; Cluster of Excellence CellNetworks, Heidelberg, Germany

12th Malaria Meeting. Bonn, 14.-15.11.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc14mal15

doi: 10.3205/14mal15, urn:nbn:de:0183-14mal156

Published: December 17, 2014

© 2014 Hentzschel et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Malaria, caused by protozoan Plasmodium parasites, remains a prevalent infectious human disease due to the lack of an efficient and safe vaccine. This is directly related to the persisting gaps in our understanding of the parasite’s interactions with the infected host, especially during the clinically-silent yet essential liver stage of Plasmodium development. Previously, we and others showed that genetically-attenuated parasites (GAP) that arrest in the liver induce sterile immunity, but only upon multiple administrations. Here, we comprehensively studied hepatic gene and miRNA expression in GAP-injected mice, and found both a broad activation of IFNγ-associated pathways and a significant increase of murine microRNA-155 (miR-155), that was especially pronounced in non-parenchymal cells including liver-resident macrophages (Kupffer cells). Remarkably, ectopic upregulation of this miRNA in the liver of mice using robust hepatotropic Adenoassociated virus 8 (AAV8) vectors enhanced GAP’s protective capacity substantially. In turn, this AAV8-mediated miR-155 expression permitted a reduction of GAP injections needed to achieve complete protection against infectious parasite challenge from previously three to only one. Our study highlights a crucial role of mammalian miRNAs in Plasmodium liver infection in vivo and concurrently implies their great potential as future immune-augmenting agents in improved vaccination regimes against malaria and other diseases.

Note: The authors Franziska Hentzschel, Christiane Hammerschmidt-Kamper, Kathleen Börner, Kirsten Heiss, Ann-Kristin Mueller, and Dirk Grimm contributed equally.