Plasmodium sporozoite–host interactions from the dermis to the hepatocyte

doi:10.1016/j.mib.2009.06.006

Current Opinion in Microbiology

Volume 12, Issue 4, August 2009, Pages 401-407

https://doi.org/10.1016/j.mib.2009.06.006 Get rights and content

Sporozoites are the infective stage of the malaria parasite. They are deposited in the skin by infected Anopheles mosquitoes and must penetrate cell barriers in the skin and liver sinusoid to reach their target cell, the hepatocyte, where they enter in a vacuole and begin development into the next life cycle stage, the exoerythrocytic form. Recent advances in our understanding of sporozoite biology in the dermal inoculation site, the role of cell traversal and the mechanism by which sporozoites productively invade hepatocytes will be highlighted in this review.

Section snippets

Plasmodium sporozoites: the same but different

Apicomplexa is a phylum of obligate intracellular protists to which Plasmodium and other human pathogens such as Toxoplasma and Cryptosporidium belong. The invasive stages of these protists, called zoites, are structurally similar, possessing an apical ring of microtubules and specialized secretory organelles called micronemes and rhoptries. Work with Plasmodium merozoites shows that they invade cells in distinct stages, beginning with initial reversible attachment followed by irreversible

Sporozoite inoculation into and exit from the dermis

Recent studies from several groups have clearly established that there is a skin stage of malaria infection (reviewed in [7]). Sporozoites are inoculated into the dermis by infected mosquitoes and contrary to the widely accepted notion that they rapidly leave the injection site, recent studies have shown that the majority of sporozoites that successfully reach the liver, take between one and three hours to leave [8•, 9•]. On average, 100 sporozoites are injected by a single infected mosquito [10

Crossing the liver sinusoid

After exiting the dermis and entering the blood circulation, sporozoites are arrested in the liver where they must traverse the sinusoidal barrier to access hepatocytes. The liver sinusoid is composed of fenestrated endothelial cells and Kupffer cells, which are resident macrophages. The endothelial cell fenestrae are too small to allow for free passage of sporozoites; therefore, sporozoites must migrate through sinusoidal cells to access the liver parenchyma on the other side. The importance

Switching from a migratory to an invasive phenotype

How do sporozoites know they have contacted their target cell and switch from a migratory to an invasive phenotype? This is an area of some controversy. Initial studies on cell traversal raised the possibility that there is no liver-specific signal that initiates the invasion process but that after traversing a number of cells, repeated exposure to the intracellular environment activates sporozoites for invasion [22]. Thus cell traversal in and of itself is sufficient for activation for

Invasion of hepatocytes

Invasion by Apicomplexan zoites is an active process that requires the coordinated release of proteins from apical organelles (reviewed in [26]). Furthermore, exocytosis of apical organelles is stimulated by the mobilization of intracellular calcium and many secreted proteins contain cell-adhesive domains that function in zoite–host interactions [22, 26]. Several adhesins of Plasmodium merozoites and Toxoplasma tachyzoites are proteolytically processed after their secretion onto the zoite

Conclusion

Recent data suggest that the process of target cell invasion by Plasmodium sporozoites is broadly similar to the process in their more well-studied cousins, Toxoplasma tachyzoites, in that it probably involves regulated exocytosis and the formation of a tight junction between host and parasite [2•, 3••, 22]. Nonetheless, the sporozoite's journey in the mammalian host dictates added layers of complexity and regulation. Its ability to migrate through nonpermissive cells [2•, 14] and to switch

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

The authors would like to thank Brandy Bennett and Dr. Marcelo Jacobs-Lorena for their helpful critiques of the manuscript and to acknowledge support from the National Institutes of Health (R01 AI056840).

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Plasmodium sporozoite–host interactions from the dermis to the hepatocyte

Section snippets

Plasmodium sporozoites: the same but different

Sporozoite inoculation into and exit from the dermis

Crossing the liver sinusoid

Switching from a migratory to an invasive phenotype

Invasion of hepatocytes

Conclusion

References and recommended reading

Acknowledgements

Trends Microbiol

Cell Host Microbe

Cell

Trends Cell Biol

Future Microbiol

Nat Med

Cell Microbiol

Nat Med

Mol Biochem Parasitol

J Exp Med

J Biol Chem

Proc Natl Acad Sci U S A

PLoS Path

PLoS Path

Parasitol Int

PLoS Path

Proc Natl Acad Sci U S A

Host cell entry by apicomplexa parasites requires actin polymerization in the host cell

Cell Host Microbe

TRAP is necessary for gliding motility and infectivity of Plasmodium sporozoites

Cell

Plasmodium sporozoites trickle out of the injection site

Cell Microbiol

Quantitative dynamics of Plasmodium yoelii sporozoite transmission by infected Anopheline mosquitoes feeding on vertebrate hosts

Infec Immun

Direct microscopic quantification of dynamics of Plasmodium berghei sporozoite transmission from mosquitoes to mice

Infect Immun

Intravital microscopy demonstrating antibody-mediated immobilisation of Plasmodium berghei sporozoites injected into skin by mosquitoes

Int J Parasitol

CD8(+) T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes

Nat Med

Migration of Plasmodium sporozoites through cells before infection

Science

Cell-passage activity is required for the malarial parasite to cross the liver sinusoidal cell layer

PLoS Biol