Infestation <i>in vitro</i> d’hepatocytes humains par des sporozoites de <i>Plasmodium vivax :</i> schizogonie et libération de mérozoïtes infestants pour des hématies humaines

Mazier, Dominique; Landau, I.; Miltgen, F; Druilhe, Pierre; Guguen‐Guillouzo, Christiane; Baccam, D.; Baxter, J; Gentilini, M

doi:10.1051/parasite/1983584405

Cited by 11 publications

(8 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At the COOH terminus, truncated peptides had full activity until the isoleucine at position 296 was removed. Complete loss of target sensitization occurred with 10 1 Spleen cells from sporozoite immunized BALB/c mice were cultured with peptide 19 (amino acids 281-300) and then tested in a CTL assay against targets in the presence of each of the nested peptides at several concentrations.…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes.

Weiss

Mellouk

Houghten

et al. 1990

The Journal of Experimental Medicine

201

View full text Add to dashboard Cite

When a person is infected with malaria by the bite of a mosquito, sporozoites travel through the bloodstream and enter hepatocytes. The parasite develops within the liver cell for days to weeks, and during this period there are no symptoms. Only after the liver stage parasites mature, and merozoites are released to invade red blood cells, do the fevers, chills and lethal complications of malaria begin. Thus, a vaccine aimed at sporozoites or liver stage parasites could eliminate malaria infections before clinical disease appears.Immunization with radiation-attenuated sporozoites can protect rodents and humans against live sporozoite challenge (1, 2). One hypothesis is that this protective immunity is mediated by cytotoxic T cells directed against malaria antigens on the infected hepatocyte . Several recently published experiments give support to this idea. Immune animals became susceptible to sporozoite infection if they were depleted of their CD8+ T cells (3, 4), but the antigens recognized by these cells and their site and mode of action were not determined. Infiltrates with CD8+ and CD4' T cells and other cellular elements were found in the livers of immune animals after challenge with sporozoites and these infiltrates formed after the transfer of immune CD8 + cells (5). Unfractionated spleen cells from immune animals eliminated malaria-infected hepatocytes from in vitro culture (5), but the active cell types and the targeted parasite antigens were not identified . A very recent study showed that mice were protected by adoptive transfer of cloned CD8+ T cells specific for an epitope on the Plasmodium berghei circumsporozoite (CS) 1 protein (6). However, it was not shown that these cells were attacking infected hepatocytes directly, or releasingThe opinions and assertions herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the U. S. Navy or the naval service at large.

show abstract

Section: Resultsmentioning

confidence: 99%

Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes.

Weiss

Mellouk

Houghten

et al. 1990

The Journal of Experimental Medicine

201

View full text Add to dashboard Cite

show abstract

“…However, an in vitro model is necessary in order to screen large numbers of new compounds for hypnozoiticidal activity. Hopes to achieve this were raised with the establishment of in vitro cultured hepatic stages of P. vivax [11] , [12] and then P. cynomolgi [13] , [14] in their respective primary host hepatocytes. In parallel, P. vivax hepatic stage maturation was obtained in the hepatoma cell line HepG2-A16 [15] .…”

Section: Introductionmentioning

confidence: 99%

Towards an In Vitro Model of Plasmodium Hypnozoites Suitable for Drug Discovery

et al. 2011

View full text Add to dashboard Cite

BackgroundAmongst the Plasmodium species in humans, only P. vivax and P. ovale produce latent hepatic stages called hypnozoites, which are responsible for malaria episodes long after a mosquito bite. Relapses contribute to increased morbidity, and complicate malaria elimination programs. A single drug effective against hypnozoites, primaquine, is available, but its deployment is curtailed by its haemolytic potential in glucose-6-phosphate dehydrogenase deficient persons. Novel compounds are thus urgently needed to replace primaquine. Discovery of compounds active against hypnozoites is restricted to the in vivo P. cynomolgi-rhesus monkey model. Slow growing hepatic parasites reminiscent of hypnozoites had been noted in cultured P. vivax-infected hepatoma cells, but similar forms are also observed in vitro by other species including P. falciparum that do not produce hypnozoites.Methodology P. falciparum or P. cynomolgi sporozoites were used to infect human or Macaca fascicularis primary hepatocytes, respectively. The susceptibility of the slow and normally growing hepatic forms obtained in vitro to three antimalarial drugs, one active against hepatic forms including hypnozoites and two only against the growing forms, was measured.ResultsThe non-dividing slow growing P. cynomolgi hepatic forms, observed in vitro in primary hepatocytes from the natural host Macaca fascicularis, can be distinguished from similar forms seen in P. falciparum-infected human primary hepatocytes by the differential action of selected anti-malarial drugs. Whereas atovaquone and pyrimethamine are active on all the dividing hepatic forms observed, the P. cynomolgi slow growing forms are highly resistant to treatment by these drugs, but remain susceptible to primaquine.ConclusionResistance of the non-dividing P. cynomolgi forms to atovaquone and pyrimethamine, which do not prevent relapses, strongly suggests that these slow growing forms are hypnozoites. This represents a first step towards the development of a practical medium-throughput in vitro screening assay for novel hypnozoiticidal drugs.

show abstract

“…After aseptic dissection, salivary glands were homogenized in a glass grinder and diluted in culture medium or sterile phosphate-buffered saline (PBS) (14).…”

Section: Parasitesmentioning

confidence: 99%

TNF inhibits malaria hepatic stages in vitro via synthesis of IL-6

Nüssler¹,

Pied²,

Goma³

et al. 1991

Int Immunol

View full text Add to dashboard Cite

We examined the capacity of murlne recomblnant tumor necrosis factor (rmTNF) to induce an inhibitory effect at the hepatic stage on malaria induced by Plasmodium yoelii sporozoltes. When injected three times, 1.0 /ig of rmTNF was found to protect 78% of mice against a sporozolte challenge. In contrast, whatever the dose and the schedule of administration, no inhibition was observed when purified hepatocyte cultures were infected with P. yoelii. The addition of nonparenchymal hepatic cells to hepatocyte cultures restored the capacity of TNF to modulate hepatic stage development, leading to up to 44% Inhibition. Antibodies to Interleukin 6 reversed the anti-parasite activity in the co-culture system.

show abstract

Infestation in vitro d’hepatocytes humains par des sporozoites de Plasmodium vivax : schizogonie et libération de mérozoïtes infestants pour des hématies humaines

Cited by 11 publications

References 1 publication

Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes.

Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes.

Towards an In Vitro Model of Plasmodium Hypnozoites Suitable for Drug Discovery

TNF inhibits malaria hepatic stages in vitro via synthesis of IL-6

Contact Info

Product

Resources

About