Differential antibody responses to Plasmodium falciparum glycosylphosphatidylinositol anchors in patients with cerebral and mild malaria

Perraut, Ronald; Diatta, Bakary; Marrama, Laurence; Garraud, Olivier; Jambou, Ronan; Longacre, Shirley; Gowda, Raghavendra; Dièye, Alioune; Gowda, D. Channe

doi:10.1016/j.micinf.2005.01.002

Cited by 34 publications

(44 citation statements)

References 24 publications

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“…High levels of the anti‐GPI antibodies have been correlated with resistance to clinical symptoms, such as anemia and fever 19, and hence these antibodies were suggested to be an important factor in the protective immunity to malaria 8, 11. Consistent with these results, lower levels of anti‐GPI were observed among Senegalese adults with cerebral malaria compared to individuals with uncomplicated malaria 14. However, the results presented here indicate the absence of significant differences either in prevalence or the levels of anti‐GPI IgGs between SM and MM groups.…”

Section: Discussionmentioning

confidence: 57%

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Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis

Mbengué

Niang

et al. 2015

Immunity, Inflammation and Disease

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Pro‐inflammatory cytokines induced by glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum contribute to malaria pathogenesis and hence, the naturally acquired anti‐GPI antibody thought to provide protection against severe malaria (SM) by neutralizing the stimulatory activity of GPIs. In previous studies, the anti‐GPI antibody levels increased with age in parallel with the development of acquired immunity, and high levels of anti‐GPI antibodies were associated with mild malaria (MM) cases. In the present study, the relationship between the levels of pro‐inflammatory cytokines and anti‐GPI IgG antibody responses, parasitemia, and the clinical outcomes were evaluated in SM and mild malaria (MM) patients. Sera from a total of 110 SM and 72 MM cases after excluding of ineligible patients were analyzed for the levels of anti‐GPI antibodies, IgG subclasses, and cytokine responses by ELISA. While the total anti‐GPI antibody levels were similar in overall SM and MM groups, they were significantly higher in surviving SM patients than in fatal SM cases. In the case of cytokines, the TNF‐α and IL‐6 levels were significantly higher in SM compared to MM, whereas the IL‐10 levels were similar in both groups. The data presented here demonstrate that high levels of the circulatory pro‐inflammatory, TNF‐α, and IL‐6, are indicators of malaria severity, whereas anti‐inflammatory cytokine IL‐10 level does not differentiate SM and MM cases. Further, among SM patients, relatively low levels of anti‐GPI antibodies are indicators of fatal outcomes compared to survivors, suggesting that anti‐GPI antibodies provide some level of protection against SM fatality.

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Section: Discussionmentioning

confidence: 57%

“…A possible explanation for these contrasting results is that the recruitment of severe urban malaria is highly heterogenic regarding the initial onset of the infection and the delay before hospitalization in the severe cases. We had previously reported that delay of admission appeared as significantly increased SM 14, 26.…”

Section: Discussionmentioning

confidence: 90%

Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis

Mbengué

Niang

et al. 2015

Immunity, Inflammation and Disease

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“…Though the proinflammatory potential of GPI molecules was amply documented in different parasitic infections including Chagas' disease (13), leishmaniasis (14), trypanosomiasis (15), and malaria (16), so far compelling evidence for a relationship between the proinflammatory properties and disease-inducing potential of parasite-derived GPIs was provided only for malaria. In the first instance, adults who acquired resistance to clinical malaria manifested persistently increased levels of serum anti-GPI Abs, whereas susceptible patients that suffered from malaria-associated anemia and fever, lacked an anti-GPI Ab response (17,18) suggesting a protective role of anti-GPI Abs against clinical malaria. Second, a GPI carbohydrate core-based vaccine that conferred partial protection to malaria-associated pathology was designed (19).…”

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confidence: 99%

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

Stijlemans

Baral

Guilliams

et al. 2007

The Journal of Immunology

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The GPI-anchored trypanosome variant surface glycoprotein (VSG) triggers macrophages to produce TNF, involved in trypanosomiasis-associated inflammation and the clinical manifestation of sleeping sickness. Aiming at inhibiting immunopathology during experimental Trypanosoma brucei infections, a VSG-derived GPI-based treatment approach was developed. To achieve this, mice were exposed to the GPI before an infectious trypanosome challenge. This GPI-based strategy resulted in a significant prolonged survival and a substantial protection against infection-associated weight loss, liver damage, acidosis, and anemia; the latter was shown to be Ab-independent and correlated with reduced macrophage-mediated RBC clearance. In addition, GPI-based treatment resulted in reduced circulating serum levels of the inflammatory cytokines TNF and IL-6, abrogation of infection-induced LPS hypersensitivity, and an increase in circulating IL-10. At the level of trypanosomiasis-associated macrophage activation, the GPI-based treatment resulted in an impaired secretion of TNF by VSG and LPS pulsed macrophages, a reduced expression of the inflammatory cytokine genes TNF, IL-6, and IL-12, and an increased expression of the anti-inflammatory cytokine gene IL-10. In addition, this change in cytokine pattern upon GPI-based treatment was associated with the expression of alternatively activated macrophage markers. Finally, the GPI-based treatment also reduced the infection-associated pathology in Trypanosoma congolense and Trypanosoma evansi model systems as well as in tsetse fly challenge experiments, indicating potential field applicability for this intervention strategy.

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“…A monoclonal antibody to P. falciparum GPIs has been reported to neutralize the tumor necrosis factor alpha (TNF-␣)-inducing activity of GPIs, suggesting that naturally elicited anti-GPI antibodies can provide protection against malaria pathogenesis (13). During the past few years, we and others have shown that people in areas where malaria is endemic produce anti-GPI antibodies in an age-dependent manner (2,3,5,8,10,11). Adults and adolescents with protective immunity to malaria have persistently high levels of antibodies, whereas children aged Ͻ3 years either lack or have low levels of antibody.…”

mentioning

confidence: 99%

Naturally Elicited Antibodies to Glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum Require Intact GPI Structures for Binding and Are Directed Primarily against the Conserved Glycan Moiety

et al. 2006

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Immunization with a synthetic glycan corresponding to Plasmodium falciparum glycosylphosphatidylinositols (GPIs) has been proposed as a vaccination strategy against malaria. We investigated the structural requirements for binding of naturally elicited anti-GPI antibodies to parasite GPIs. The data show that anti-GPI antibody binding requires intact GPI structures and that the antibodies are directed predominantly against GPIs with a conserved glycan structure with three mannoses and marginally against the terminal fourth mannose. The results provide valuable insight for exploiting GPIs for the development of malaria vaccines.

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Differential antibody responses to Plasmodium falciparum glycosylphosphatidylinositol anchors in patients with cerebral and mild malaria

Cited by 34 publications

References 24 publications

Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis

Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

Naturally Elicited Antibodies to Glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum Require Intact GPI Structures for Binding and Are Directed Primarily against the Conserved Glycan Moiety

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