Killing the competition: a theoretical framework for liver-stage malaria



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Arias, Clemente F. and Acosta, Francisco J. and Fernández Arias, Cristina (2022) Killing the competition: a theoretical framework for liver-stage malaria. Open Biology, 12 (3). pp. 1-13. ISSN 2046-2441

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The first stage of malaria infections takes place inside the host's hepatocytes. Remarkably, Plasmodium parasites do not infect hepatocytes immediately after reaching the liver. Instead, they migrate through several hepatocytes before infecting their definitive host cells, thus increasing their chances of immune destruction. Considering that malaria can proceed normally without cell traversal, this is indeed a puzzling behaviour. In fact, the role of hepatocyte traversal remains unknown to date, implying that the current understanding of malaria is incomplete. In this work, we hypothesize that the parasites traverse hepatocytes to actively trigger an immune response in the host. This behaviour would be part of a strategy of superinfection exclusion aimed to reduce intraspecific competition during the blood stage of the infection. Based on this hypothesis, we formulate a comprehensive theory of liver-stage malaria that integrates all the available knowledge about the infection. The interest of this new paradigm is not merely theoretical. It highlights major issues in the current empirical approach to the study of Plasmodium and suggests new strategies to fight malaria.

Item Type:Article
Uncontrolled Keywords:Plasmodium; superinfection exclusion; liver-stage malaria; antimalarial vaccines; concomitant immunity
Subjects:Medical sciences > Medicine > Immunology
ID Code:75230
Deposited On:21 Oct 2022 14:03
Last Modified:07 Nov 2022 08:35

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