Journal Article

The silent path to thousands of merozoites: the Plasmodium liver stage

Mota, Maria M., Rodriguez, Ana, Prudêncio, Miguel

2006

Overview

Key Points Malaria is a major health problem, mainly in sub-Saharan Africa and in some parts of Asia and south America. Each year there are about 600 million new clinical cases and at least one million individuals, mostly children, die from malaria; in other words there is a death caused by malaria every 30 seconds. Successful malaria transmission to the mammalian host is established through sporozoite infection of the liver. The importance of the liver stages, owing to its status as an obligatory step in infection, makes this stage an attractive target for both drug and vaccine development. In recent years, our understanding of Plasmodium sporozoite biology, the interactions of sporozoites with different host cells and their establishment in the liver, has increased through the implementation of new technologies that allow researchers to follow the progress of the parasites from the site of injection to the liver. Plasmodium sporozoites are deposited in the skin of their vertebrate host by the bite of an infected female Anopheles mosquito. A proportion of these parasites are drained to the lymph nodes, where they are trapped, whereas the majority find a blood vessel and travel in the peripheral blood circulation until they reach the liver sinusoids. Once arrested in the liver sinusoids, the sporozoites cross the sinusoidal wall and migrate through several hepatocytes by breaching their plasma membrane, before they infect a final hepatocyte with the formation of a parasitophorous vacuole. The intrahepatic form of the parasite grows and multiplies in this vacuole, producing thousands of merozoites per sporozoite. This Review summarizes our current knowledge on this stage of the Plasmodium life cycle. The liver stage of Plasmodium infection constitutes an appealing target for the development of vaccines or prophylatic drugs as this step in the life cycle is obligatory but occurs before the onset of pathology. This Review summarizes the current knowledge on this stage of the Plasmodium life cycle. Plasmodium sporozoites are deposited in the skin of their vertebrate hosts through the bite of an infected female Anopheles mosquito. Most of these parasites find a blood vessel and travel in the peripheral blood circulation until they reach the liver sinusoids. Once there, the sporozoites cross the sinusoidal wall and migrate through several hepatocytes before they infect a final hepatocyte, with the formation of a parasitophorous vacuole, in which the intrahepatic form of the parasite grows and multiplies. During this period, each sporozoite generates thousands of merozoites. As the development of Plasmodium sporozoites inside hepatocytes is an obligatory step before the onset of disease, understanding the parasite's requirements during this period is crucial for the development of any form of early intervention. This Review summarizes our current knowledge on this stage of the Plasmodium life cycle.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Anopheles / Aquatic insects / Biomedical and Life Sciences / Blood circulation / Blood parasites / Blood vessels / Circulatory system / Disease transmission / Drug development / Exocrine glands / Hepatocytes / Host-Parasite Interactions / Humans / Infections / Infectious Diseases / Life cycles / Life Sciences / Liver / Liver - parasitology / Lymph nodes / Malaria / Medical Microbiology / Merozoites / Microbiology / Microscopy / Mosquitoes / Motility / Parasites / Parasitology / Parasitophorous vacuole / Peripheral blood / Plasmodium / Plasmodium - physiology / review-article / Sine waves / Skin / Sporozoites / Sporozoites - physiology / Vaccine development / Vaccines / Vector-borne diseases / Vertebrates / Virology