A malaria heat‐shock‐like determinant expressed on the infected hepatocyte surface is the target of antibody‐dependent cell‐mediated cytotoxic mechanisms by nonparenchymal liver cells

Rénia, Laurent; Mattei, Denise; Goma, Joseph; Pied, Sylviane; Dubois, Philippe; Miltgen, F; Nüssler, Andreas K.; Matile, Hugues; Ménégaux, Fabrice; Gentilini, M; Mazier, Dominique

doi:10.1002/eji.1830200706

Cited by 107 publications

(70 citation statements)

References 24 publications

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“…2A). The anti-MAEBL sera were also tested on methanol-fixed malaria liver-stage parasites as previously described (20). All anti-MAEBL but no FIG.…”

Section: Resultsmentioning

confidence: 99%

“…The dilutions of the primary sera were 1:500 to 1:800. Serum reactivity was tested by an immunofluorescence assay using methanol-fixed midgut or salivary gland sporozoites, previously air dried on microscope slides, or malaria liver-stage parasites as previously described (20).…”

Section: Methodsmentioning

confidence: 99%

“…The cultures were incubated for 3 h and washed, and fresh medium was added. After 24 h the medium was changed once and incubated another 24 h. The schizonts in each culture well were stained with anti-PfHSP70 antibodies to count hepatic schizonts (20). Inhibition was determined by counting the number of hepatic schizonts in the test cultures relative the number in cultures with preimmune serum.…”

Section: Methodsmentioning

confidence: 99%

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Antibodies against MAEBL Ligand Domains M1 and M2 Inhibit Sporozoite Development In Vitro

Preiser¹,

Rénia

Singh

et al. 2004

Infect Immun

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MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical organelle protein is structurally similar to the ebl erythrocyte binding proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are similar to part of the extracellular domain of apical membrane antigen 1 and not the Duffy binding-like domain. Although midgut and salivary gland sporozoites are morphologically similar, salivary gland sporozoites undergo a period of new gene expression after infecting the salivary glands, display distinct phenotypic differences, and are more infectious for the mammalian host. The objectives of this project were to determine the molecular form of MAEBL in the infectious salivary gland sporozoites and whether the ligand has a role in the sporozoite development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is newly expressed in salivary gland sporozoites and in a form distinct from what is present in the midgut sporozoites or present in erythrocytic stages. Both ligand domains (M1 and M2) were expressed as part of a full-length membrane form of MAEBL in the salivary gland sporozoites in contrast to the other stages that retain only the M2 ligand domain as part of the membrane form of the protein. Antisera developed against the cysteine-rich regions of the extracellular portion of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro. Together these data indicate that MAEBL has a role in this third developmental stage in the life cycle of the malaria parasite. Thus, MAEBL is another target for pre-erythrocytic-stage vaccine development against malaria parasites.Malaria is one of the most serious human diseases, causing several million deaths and clinical illness in hundreds of millions of people every year. Infection is spread from person to person by the bite of a Plasmodium-infected anopheline mosquito. Sporozoites injected by the mosquito must infect and develop in a hepatocyte, which can then initiate the bloodstage infection that causes the severe pathogenesis of malaria. Molecules in the apical organelles and on the surface of malaria sporozoites play a role in sporozoite motility and target this infective stage to the liver. The completion of the Plasmodium falciparum genome has provided the basis for the identification of many proteins in sporozoites (5, 12), but very few of these proteins are characterized for their function in sporozoite infectivity and development in the liver. Proteomic and transcript analyses have identified a number of apical organelle and membraneassociated proteins expressed both in sporozoites and merozoites, with many belonging to molecular families conserved among the diverse species of Plasmodium (3,5,7,19,(22)(23)(24).The circumsporozoite protein (CSP) and to a lesser extent the thrombospondin-related anonymous protein (TRAP, or sporozoite surface protein 2 [SSP2]) have been the focus of most research on the sporozoite stages. CSP ...

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“…2A). The anti-MAEBL sera were also tested on methanol-fixed malaria liver-stage parasites as previously described (20). All anti-MAEBL but no FIG.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Antibodies against MAEBL Ligand Domains M1 and M2 Inhibit Sporozoite Development In Vitro

Preiser¹,

Rénia

Singh

et al. 2004

Infect Immun

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“…We do have preliminary evidence that HSP70 is indeed secreted by T. gondii; analysis of precipitated proteins separated by two-dimensional electrophoresis and probed with a parasite specific anti-HSP70 Ab detected parasite HSP70 in the culture supernatant at 4 h postinfection (data not shown). Furthermore, a number of examples from other parasites have described extracellular HSP70; for example, a 72-kDa Plasmodium falciparum HSP related to the 78-kDa glucose-regulated stress protein of mammals called Pfgrp (27) was detected in sera of people exposed to this parasite (28), and is expressed on the surface of infected hepatocytes (29).…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Protein 70 Is a Potential Virulence Factor in MurineToxoplasmaInfection Via Immunomodulation of Host NF-κB and Nitric Oxide

Dobbin

Smith

Johnson

2002

The Journal of Immunology

106

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“…BALB/c hepatocytes were prepared as previously described, with minor modifications (17). Cells were isolated by collagenase perfusion (Roche) of liver fragments and were further purified over a 60% Percoll gradient (Pharmacia Biotech, Uppsala, Sweden).…”

Section: Culture Of Malaria Lssmentioning

confidence: 99%

Protective T Cell Immunity against Malaria Liver Stage after Vaccination with Live Sporozoites under Chloroquine Treatment

Belnoue

Costa

Frankenberg

et al. 2004

The Journal of Immunology

Self Cite

211

281

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In this study we present the first systematic analysis of the immunity induced by normal Plasmodium yoelii sporozoites in mice. Immunization with sporozoites, which was conducted under chloroquine treatment to minimize the influence of blood stage parasites, induced a strong protection against a subsequent sporozoite and, to a lesser extent, against infected RBC challenges. The protection induced by this immunization protocol proved to be very effective. Induction of this protective immunity depended on the presence of liver stage parasites, as primaquine treatment concurrent with sporozoite immunization abrogated protection. Protection was not found to be mediated by the Abs elicited against pre-erythrocytic and blood stage parasites, as demonstrated by inhibition assays of sporozoite penetration or development in vitro and in vivo assays of sporozoite infectivity or blood stage parasite development. CD4+ and CD8+ T cells were, however, responsible for the protection through the induction of IFN-γ and NO.

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A malaria heat‐shock‐like determinant expressed on the infected hepatocyte surface is the target of antibody‐dependent cell‐mediated cytotoxic mechanisms by nonparenchymal liver cells

Cited by 107 publications

References 24 publications

Antibodies against MAEBL Ligand Domains M1 and M2 Inhibit Sporozoite Development In Vitro

Antibodies against MAEBL Ligand Domains M1 and M2 Inhibit Sporozoite Development In Vitro

Heat Shock Protein 70 Is a Potential Virulence Factor in MurineToxoplasmaInfection Via Immunomodulation of Host NF-κB and Nitric Oxide

Protective T Cell Immunity against Malaria Liver Stage after Vaccination with Live Sporozoites under Chloroquine Treatment

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