Role of Plasmodium berghei cGMP-dependent Protein Kinase in Late Liver Stage Development |
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Authors: | Adebola Falae Audrey Combe Anburaj Amaladoss Teresa Carvalho Robert Menard Purnima Bhanot |
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Affiliation: | From the ‡Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103 and ;§Unité de Biologie et Génétique du Paludisme, Institut Pasteur, 75724 Paris Cedex 15, France |
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Abstract: | The liver is the first organ infected by Plasmodium sporozoites during malaria infection. In the infected hepatocytes, sporozoites undergo a complex developmental program to eventually generate hepatic merozoites that are released into the bloodstream in membrane-bound vesicles termed merosomes. Parasites blocked at an early developmental stage inside hepatocytes elicit a protective host immune response, making them attractive targets in the effort to develop a pre-erythrocytic stage vaccine. Here, we generated parasites blocked at a late developmental stage inside hepatocytes by conditionally disrupting the Plasmodium berghei cGMP-dependent protein kinase in sporozoites. Mutant sporozoites are able to invade hepatocytes and undergo intracellular development. However, they remain blocked as late liver stages that do not release merosomes into the medium. These late arrested liver stages induce protection in immunized animals. This suggests that, similar to the well studied early liver stages, late stage liver stages too can confer protection from sporozoite challenge. |
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Keywords: | Genetics Immunology Organisms/Parasite Organisms/Protozoan Gene Knockout Plasmodium Development Kinase Liver Stage |
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