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iScience. 2019 Nov 22;21:603-611. doi: 10.1016/j.isci.2019.10.054. Epub 2019 Oct 31.

Plasmodium Secretion Induces Hepatocyte Lysosome Exocytosis and Promotes Parasite Entry.

Author information

1
Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue, N. Suite 500, Seattle, WA 98109, USA.
2
Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue, N. Suite 500, Seattle, WA 98109, USA; Institute of Parasitology, McGill University, Ste Anne de Bellevue, QC H9X 3V9, Canada.
3
Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue, N. Suite 500, Seattle, WA 98109, USA; Institute for Systems Biology, 401 Terry Avenue, N, Seattle, WA 98109, USA.
4
Department of Global Health, University of Washington, Harris Hydraulics Laboratory Box 357965, Seattle, WA 98195-7965, USA.
5
Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue, N. Suite 500, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Harris Hydraulics Laboratory Box 357965, Seattle, WA 98195-7965, USA.
6
Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue, N. Suite 500, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Harris Hydraulics Laboratory Box 357965, Seattle, WA 98195-7965, USA. Electronic address: alexis.kaushansky@seattlechildrens.org.

Abstract

The invasion of a suitable host hepatocyte by Plasmodium sporozoites is an essential step in malaria infection. We demonstrate that in infected hepatocytes, lysosomes are redistributed away from the nucleus, and surface exposure of lysosome-associated membrane protein 1 (LAMP1) is increased. Lysosome exocytosis in infected cells occurs independently of sporozoite traversal. Instead, a sporozoite-secreted factor is sufficient for the process. Knockdown of SNARE proteins involved in lysosome-plasma membrane fusion reduces lysosome exocytosis and Plasmodium infection. In contrast, promoting fusion between the lysosome and plasma membrane dramatically increases infection. Our work demonstrates parallels between Plasmodium sporozoite entry of hepatocytes and infection by the excavate pathogen Trypanosoma cruzi and raises the question of whether convergent evolution has shaped host cell invasion by divergent pathogens.

KEYWORDS:

Biological Sciences; Cell Biology; Microbiology Parasite; Molecular Biology; Molecular Microbiology; Parasitology

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