Role of Plasmodium berghei cGMP-dependent protein kinase in late liver stage development.
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.
Falae
Adebola
A
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA.
Combe
Audrey
A
Amaladoss
Anburaj
A
Carvalho
Teresa
T
Menard
Robert
R
Bhanot
Purnima
P
D000818:Animals; D000852:Anopheles; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000469:parasitology*; D017780:Malaria Vaccines; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009154:Mutation; D010962:Plasmodium berghei / Q000378:metabolism*; D013997:Time Factors
D017780:Malaria Vaccines; D017869:Cyclic GMP-Dependent Protein Kinases