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      Plasmodium Sporozoite Biology

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          Abstract

          Plasmodium sporozoite transmission is a critical population bottleneck in parasite life-cycle progression and, hence, a target for prophylactic drugs and vaccines. The recent progress of a candidate antisporozoite subunit vaccine formulation to licensure highlights the importance of sporozoite transmission intervention in the malaria control portfolio. Sporozoites colonize mosquito salivary glands, migrate through the skin, penetrate blood vessels, breach the liver sinusoid, and invade hepatocytes. Understanding the molecular and cellular mechanisms that mediate the remarkable sporozoite journey in the invertebrate vector and the vertebrate host can inform evidence-based next-generation drug development programs and immune intervention strategies.

          Abstract

          Malaria sporozoites are injected into the bloodstream by mosquitoes and travel to the liver, where they divide. A better understanding of this initial infection stage may lead to prophylactic drugs and vaccines.

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          Quantitative imaging of Plasmodium transmission from mosquito to mammal.

          Plasmodium, the parasite that causes malaria, is transmitted by a mosquito into the dermis and must reach the liver before infecting erythrocytes and causing disease. We present here a quantitative, real-time analysis of the fate of parasites transmitted in a rodent system. We show that only a proportion of the parasites enter blood capillaries, whereas others are drained by lymphatics. Lymph sporozoites stop at the proximal lymph node, where most are degraded inside dendritic leucocytes, but some can partially differentiate into exoerythrocytic stages. This previously unrecognized step of the parasite life cycle could influence the immune response of the host, and may have implications for vaccination strategies against the preerythrocytic stages of the parasite.
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            TRAP is necessary for gliding motility and infectivity of plasmodium sporozoites.

            Many protozoans of the phylum Apicomplexa are invasive parasites that exhibit a substrate-dependent gliding motility. Plasmodium (malaria) sporozoites, the stage of the parasite that invades the salivary glands of the mosquito vector and the liver of the vertebrate host, express a surface protein called thrombospondin-related anonymous protein (TRAP) that has homologs in other Apicomplexa. By gene targeting in a rodent Plasmodium, we demonstrate that TRAP is critical for sporozoite infection of the mosquito salivary glands and the rat liver, and is essential for sporozoite gliding motility in vitro. This suggests that in Plasmodium sporozoites, and likely in other Apicomplexa, gliding locomotion and cell invasion have a common molecular basis.
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              The silent path to thousands of merozoites: the Plasmodium liver stage.

              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.
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                Author and article information

                Journal
                Cold Spring Harb Perspect Med
                Cold Spring Harb Perspect Med
                cshperspectmed
                cshperspectmed
                Cold Spring Harbor Perspectives in Medicine
                Cold Spring Harbor Laboratory Press (Cold Spring Harbor, New York )
                2157-1422
                May 2017
                : 7
                : 5
                : a025478
                Affiliations
                [1 ]Integrative Parasitology, Center for Infectious Diseases, University of Heidelberg Medical School, 69120 Heidelberg, Germany
                [2 ]Department of Molecular Parasitology, Institute of Biology, Humboldt University Berlin, 10115 Berlin, Germany
                Author notes
                Article
                PMC5411682 PMC5411682 5411682 a025478
                10.1101/cshperspect.a025478
                5411682
                28108531
                32bfa7ce-01d2-4d1a-8c8a-fc8a3ec698f6
                Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved
                History
                Page count
                Pages: 14
                Categories
                107
                Perspectives

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