Infection of cryopreserved adult human hepatocytes with sporozoites

Meis, Jacques F.; Rijntjes, P. J. M.; Verhave, J.P.; Ponnudurai, T.; Hollingdale, M. R.; Yap, Sing Hiem

doi:10.1016/0309-1651(85)90062-1

Cited by 11 publications

(6 citation statements)

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“…Although some attempts to infect cryopreserved human primary hepatocytes have been described in the past (Meis et al, 1985; Silvie et al, 2004), this source of hepatocytes has not been routinely adopted by the field, to date. The advantages of screening individual donor-derived cryopreserved hepatocytes is paralleled by the successful production of purified, vialed, cryopreserved sporozoites (Chattopadhyay et al, 2010; Epstein et al, 2011; Hoffman et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

A Microscale Human Liver Platform that Supports the Hepatic Stages of Plasmodium falciparum and vivax

March

Velmurugan

et al. 2013

Cell Host & Microbe

189

223

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SUMMARY The Plasmodium liver stage is an attractive target for the development of anti-malarial drugs and vaccines, as it provides an opportunity to interrupt the life cycle of the parasite at a critical early stage. However, targeting the liver stage has been difficult. Undoubtedly, a major barrier has been the lack of robust, reliable and reproducible in vitro liver stage cultures. Here, we establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in a microscale human liver platform composed of cryopreserved, micropatterned human primary hepatocytes surrounded by supportive stromal cells. Using this system, we have successfully recapitulated the full liver stage of P. falciparum including the release of infected merozoites and infection of overlaid erythrocytes, and also the establishment of small forms in late liver stages of P. vivax. Finally, we validate the potential of this platform as a tool for medium-throughput anti-malarial drug screening and vaccine development.

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Section: Discussionmentioning

confidence: 99%

A Microscale Human Liver Platform that Supports the Hepatic Stages of Plasmodium falciparum and vivax

March

Velmurugan

et al. 2013

Cell Host & Microbe

189

223

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“…We used either fresh or cryopreserved hepatocytes, both susceptible to infection with P. falciparum sporozoites (17,18). In our hands, P. falciparum sporozoite infectivity is similar in fresh and cryopreserved hepatocytes.…”

Section: Methodsmentioning

confidence: 99%

A Role for Apical Membrane Antigen 1 during Invasion of Hepatocytes by Plasmodium falciparum Sporozoites

Silvie

Franetich

Charrin

et al. 2004

Journal of Biological Chemistry

286

246

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Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and invade hepatocytes as a first and obligatory step of the parasite life cycle in man. Hepatocyte invasion involves proteins secreted from parasite vesicles called micronemes, the most characterized being the thrombospondin-related adhesive protein (TRAP). Here we investigated the expression and function of another microneme protein recently identified in Plasmodium falciparum sporozoites, apical membrane antigen 1 (AMA-1). P. falciparum AMA-1 is expressed in sporozoites and is lost after invasion of hepatocytes, and anti-AMA-1 antibodies inhibit sporozoite invasion, suggesting that the protein is involved during invasion of hepatocytes. As observed with TRAP, AMA-1 is initially mostly sequestered within the sporozoite. Upon microneme exocytosis, AMA-1 and TRAP relocate to the sporozoite surface, where they are proteolytically cleaved, resulting in the shedding of soluble fragments. A subset of serine protease inhibitors blocks the processing and shedding of both AMA-1 and TRAP and inhibits sporozoite infectivity, suggesting that interfering with sporozoite proteolytic processing may constitute a valuable strategy to prevent hepatocyte infection.

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“…This is surprising, because in both Toxoplasma and Sarcocystis parasites, the apicoplast is connected with the nucleus (Striepen et al ., ; Vaishnava et al ., ). The observation that the mitochondrion, like the apicoplast, undergoes extensive branching during schizogony contradicts earlier EM studies that described a proliferation of the mitochondrion during schizogony based on the observation of multiple mitochondrial profiles in thin section (Meis et al ., , b, c). However, this observation is not contradictory to a branched network as described by us because in thin sections a highly branched structure would also result in multiple profiles.…”

Section: The Schizont: Rapid Nuclear Division and Extensive Organellementioning

confidence: 99%

“…). During the cytomere stage, the individual units of plasma membrane are not fully separated and mitochondrial branches connect the afore‐mentioned clumps, confirming earlier EM studies on exo‐erythrocytic development of the parasite (Meis et al ., , , b, c). The cytomere stage is an intermediary parasite stage and soon after its formation, the apicoplast develops a concertinaed structure, presumably due to the constriction of the organelle at sites where fission will take place.…”

Section: The Cytomere: Generating Order Out Of Chaosmentioning

confidence: 99%

“…The first hurdle for the parasite is the PVM and it has been shown that during merozoite formation parasite proteins begin to leak into the host cell, thus demonstrating that the membrane of the PV becomes increasingly permeable before it is completely disrupted (Schmidt‐Christensen et al ., ; Sturm et al ., ). As another sign of PVM breakdown, several previous in vivo studies had already indicated that parasite and host cell material mix freely in infected cells (Movie S8) (Meis et al ., , b, c; Baer et al ., ). Very recently, live imaging of a parasite strain expressing a fluorescent PVM marker protein confirmed the breakdown of the PVM toward the end of the liver stage while the host cell membrane stays intact (Graewe et al ., in press).…”

Section: Breaking Out: Egress From the Parasitophorous Vacuolementioning

confidence: 99%

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Chronicle of a death foretold:Plasmodiumliver stage parasites decide on the fate of the host cell

Graewe

Stanway

Rennenberg³

et al. 2012

FEMS Microbiol Rev

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Protozoan parasites of the genus Plasmodium are the causative agents of malaria. Despite more than 100 years of research, the complex life cycle of the parasite still bears many surprises and it is safe to say that understanding the biology of the pathogen will keep scientists busy for many years to come. Malaria research has mainly concentrated on the pathological blood stage of Plasmodium parasites, leaving us with many questions concerning parasite development within the mosquito and during the exo-erythrocytic stage in the vertebrate host. After the discovery of the Plasmodium liver stage in the middle of the last century, it remained understudied for many years but the realization that it represents a promising target for vaccination approaches has brought it back into focus. The last decade saw many new and exciting discoveries concerning the exo-erythrocytic stage and in this review we will discuss the highlights of the latest developments in the field.

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Infection of cryopreserved adult human hepatocytes with sporozoites

Cited by 11 publications

References 0 publications

A Microscale Human Liver Platform that Supports the Hepatic Stages of Plasmodium falciparum and vivax

A Microscale Human Liver Platform that Supports the Hepatic Stages of Plasmodium falciparum and vivax

A Role for Apical Membrane Antigen 1 during Invasion of Hepatocytes by Plasmodium falciparum Sporozoites

Chronicle of a death foretold:Plasmodiumliver stage parasites decide on the fate of the host cell

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