Host cell factor CD59 restricts complement lysis of <i>Plasmodium falciparum</i>‐infected erythrocytes

Wiesner, Jochen; Jomaa, Hassan; Wilhelm, Martin; Tony, Hans‐Peter; Kremsner, Peter G.; Horrocks, Paul; Lanzer, Michael

doi:10.1002/eji.1830271034

Cited by 30 publications

(32 citation statements)

References 31 publications

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“…The relatively small contribution of complement to this early stage of infection by the blood stage parasite is perhaps a consequence of the inefficiency of complement in mediating the lysis of parasite-infected cells (14,48). These data, taken together with studies demonstrating that antibody-mediated protection in nonlethal or lethal malaria models does not require Fc receptors (31,45), suggest that there is not a prominent role for either of the major opsonophagocytic systems in host defense against a primary blood stage malaria infection in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Complement has been shown to be able to kill both human and rodent malaria parasites in vitro, at different stages in the life cycle, in the presence of specific antibodies (10,11,29). However, infected erythrocytes, in spite of their ability to activate complement, seem quite resistant to complement-mediated lysis, a phenomenon attributable in part to the presence of complement-regulatory proteins on the infected cells (14,48). Moreover, Plasmodium berghei sporozoites have been shown to be resistant to complement from their susceptible rodent hosts but not to human serum (15).…”

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Complement Contributes to Protective Immunity against Reinfection byPlasmodium chabaudi chabaudiParasites

et al. 2001

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We have studied the impact of deficiency of the complement system on the progression and control of the erythrocyte stages of the malarial parasite Plasmodium chabaudi chabaudi. C1q-deficient mice and factor B-and C2-deficient mice, deficient in the classical complement pathway and in both the alternative and classical complement activation pathways, respectively, exhibited only a slight delay in the resolution of the acute phase of parasitemia. Complement-deficient mice showed a transiently elevated level of gamma interferon (IFN-␥) in the plasma at the time of the acute parasitemia compared with that of wild-type mice. Although there was a trend for increased precursor frequencies in CD4 ؉ T cells from C1q-deficient mice producing IFN-␥ in response to malarial antigens in vitro, intracellular cytokine staining of spleen cells ex vivo showed no difference in the numbers of IFN-␥ ؉ splenic CD4 ؉ and CD8 ؉ cells. In contrast, C1q-deficient animals were significantly more susceptible to a second challenge with the same parasite. C1q-deficient animals showed a reduced level of anti-malarial immunoglobulin G2a (IgG2a) antibody 100 days after primary infection. However, following a significantly higher parasitemia, C1q-deficient mice had increased levels of IgM and IgG2a anti-malarial antibodies. In summary, this study indicates that while complement plays only a minor role in the control of the acute phase of parasitemia of a primary infection, it does contribute to parasite control in reinfection.

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Section: Discussionmentioning

confidence: 99%

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Complement Contributes to Protective Immunity against Reinfection byPlasmodium chabaudi chabaudiParasites

et al. 2001

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“…We therefore investigated malarial infection and vacuolar uptake of raft markers in PNH cells as compared with normal cells. Previous studies have indicated that PNH cells are invaded by the malaria parasite (35,36). However, the issue of intraerythrocytic growth of the parasite within the vacuole and the uptake of DRM proteins and lipids during infection was not examined.…”

Section: Movement Of Erythrocyte Raft Proteins and Lipids Into A Malamentioning

confidence: 99%

The Role of Cholesterol and Glycosylphosphatidylinositol-anchored Proteins of Erythrocyte Rafts in Regulating Raft Protein Content and Malarial Infection

Samuel

Mohandas²,

Harrison

et al. 2001

Journal of Biological Chemistry

173

152

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Human erythrocytes are terminally differentiated, nonendocytic cells that lack all intracellular organelles. Here we show that their plasma membranes contain detergentresistant membrane rafts that constitute a small fraction (4%) of the total membrane protein, with a complex mixture of proteins that differentially associate with rafts. Depletion of raft-cholesterol abrogates association of all proteins with no significant effect on cholesterol:protein ratios in the rest of the membrane, lipid asymmetry, deformability, or transport properties of the bilayer, indicating that cholesterol is critical for protein assembly into rafts and suggesting that rafts have little influence on several erythrocyte functions. Erythrocytes from patients with paroxysmal nocturnal hemoglobinuria, which lack glycosylphosphatidylinositol-anchored proteins, show significant elevation in raft-cholesterol but no increase in raft protein association, suggesting that raft assembly does not require glycosylphosphatidylinositol-anchored proteins, raft proteins do not bind directly to cholesterol, and only threshold levels of raft-cholesterol are critical for protein recruitment. Loss of glycosylphosphatidylinositol-anchored proteins had no effect on erythrocytic infection by malarial parasite or movement of raft markers into the parasite's vacuole. However, infection is blocked following raft-cholesterol disruption, suggesting that erythrocyte rafts can be functionally exploited and providing the first evidence for the involvement of host rafts in an apicomplexan infection.

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“…CD59 is a principal regulatory protein of complement attack [17]. Weisner et al [28] found that despite the activation of all lytic complement factors, no complement-mediated lysis of RBC occurred in the presence of functional intrinsic CD59. Because CD59 levels do not change significantly during malarial anaemia, this probably limits complement-mediated lysis.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of complement occurs in a step-wise fashion, and each regulatory protein acts at a different step in the cascade. CD55 acts at the initial enzymatic step to prevent the activation of C3 to C3b by accelerating the dissociation of the C3 convertase C4-2a and C3bBb [28-30]. CD59 prevents formation of polymeric C9 complex at the final step of MAC assembly [31].…”

Section: Discussionmentioning

confidence: 99%

Early and extensive CD55 loss from red blood cells supports a causal role in malarial anaemia

Gwamaka

Fried

Domingo

et al. 2011

Malar J

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BackgroundLevels of complement regulatory proteins (CrP) on the surface of red blood cells (RBC) decrease during severe malarial anaemia and as part of cell ageing process. It remains unclear whether CrP changes seen during malaria contribute to the development of anaemia, or result from an altered RBC age distribution due to suppressive effects of malaria on erythropoiesis.MethodsA cross sectional study was conducted in the north-east coast of Tanzania to investigate whether the changes in glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins (CD55 and CD59) contributes to malaria anaemia. Blood samples were collected from a cohort of children under intensive surveillance for Plasmodium falciparum parasitaemia and illness. Levels of CD55 and CD59 were measured by flow cytometer and compared between anaemic (8.08 g/dl) and non- anaemic children (11.42 g/dl).ResultsLevels of CD55 and CD59 decreased with increased RBC age. CD55 levels were lower in anaemic children and the difference was seen in RBC of all ages. Levels of CD59 were lower in anaemic children, but these differences were not significant. CD55, but not CD59, levels correlated positively with the level of haemoglobin in anaemic children.ConclusionThe extent of CD55 loss from RBC of all ages early in the course of malarial anaemia and the correlation of CD55 with haemoglobin levels support the hypothesis that CD55 may play a causal role in this disorder.

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Host cell factor CD59 restricts complement lysis of Plasmodium falciparum‐infected erythrocytes

Cited by 30 publications

References 31 publications

Complement Contributes to Protective Immunity against Reinfection byPlasmodium chabaudi chabaudiParasites

Complement Contributes to Protective Immunity against Reinfection byPlasmodium chabaudi chabaudiParasites

The Role of Cholesterol and Glycosylphosphatidylinositol-anchored Proteins of Erythrocyte Rafts in Regulating Raft Protein Content and Malarial Infection

Early and extensive CD55 loss from red blood cells supports a causal role in malarial anaemia

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