Three Is a Crowd – New Insights into Rosetting in Plasmodium falciparum

Yam, Xue Yan; Niang, Makhtar; Madnani, Kripa Gopal; Preiser, Peter R.

doi:10.1016/j.pt.2016.12.012

Cited by 40 publications

(38 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, it was shown that mollusk HS inhibited P-selectin activity, 12 which can function as a receptor for PfEMP- 1( 20 and is known to contribute to malaria pathogenesis. 3 Despite displaying comparable activity to heparin, HS does not cause relevant bleeding. Previously, we showed that mollusk HS has reduced anticoagulant activity compared with porcine heparin.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A new heparan sulfate from the mollusk Nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of Plasmodium falciparum

Bastos

Albrecht

Gomes

et al. 2019

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

BACKGROUND Despite treatment with effective antimalarial drugs, the mortality rate is still high in severe cases of the disease, highlighting the need to find adjunct therapies that can inhibit the adhesion of Plasmodium falciparum -infected erythrocytes (Pf-iEs). OBJECTIVES In this context, we evaluated a new heparan sulfate (HS) from Nodipecten nodosus for antimalarial activity and inhibition of P. falciparum cytoadhesion and rosetting. METHODS Parasite inhibition was measured by SYBR green using a cytometer. HS was assessed in rosetting and cytoadhesion assays under static and flow conditions using Chinese hamster ovary (CHO) and human lymphatic endothelial cell (HLEC) cells expressing intercellular adhesion molecule-1 (ICAM1) and chondroitin sulfate A (CSA), respectively. FINDINGS This HS inhibited merozoite invasion similar to heparin. Moreover, mollusk HS decreased cytoadherence of P. falciparum to CSA and ICAM-1 on the surface of endothelial cells under static and flow conditions. In addition, this glycan efficiently disrupted rosettes. CONCLUSIONS These findings support a potential use for mollusk HS as adjunct therapy for severe malaria.

show abstract

Section: Resultsmentioning

confidence: 99%

“…These events may lead to occlusion of the microvasculature of vital organs, contributing to the pathogenesis of severe malaria. 2 , 3 …”

mentioning

confidence: 99%

A new heparan sulfate from the mollusk Nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of Plasmodium falciparum

Bastos

Albrecht

Gomes

et al. 2019

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

“…Notably, some of RIFINs and STEVORs are also expressed in gametocytes. For reviews on these antigens, see (Wahlgren et al, ; Yam, Niang, Madnani, & Preiser, ).…”

Section: Renovation Of Host Erythrocytes Helps To Secure the Propagatmentioning

confidence: 99%

“…Notably, some of RIFINs and STEVORs are also expressed in gametocytes. For reviews on these antigens, see (Wahlgren et al, 2017;Yam, Niang, Madnani, & Preiser, 2017). Several other P. falciparum effector proteins such as knobassociated histidine rich protein (KAHRP), ring-infected erythrocyte surface antigen (RESA), and the Plasmodium helical interspersed subtelomeric-domain proteins (PHIST) modulate the cytoskeleton to increase the rigidity of the erythrocyte to promote endothelial attachment and prevent parasite clearance through the spleen (reviewed in Spillman, Beck, & Goldberg, 2015;de Koning-Ward et al, 2016;Figure 1).…”

mentioning

confidence: 99%

Illuminating how malaria parasites export proteins into host erythrocytes

Matthews

Pitman

Koning-Ward

2019

Cellular Microbiology

View full text Add to dashboard Cite

Abstact Plasmodium parasites that cause the disease malaria have developed an elaborate trafficking pathway to facilitate the export of hundreds of effector proteins into their host cell, the erythrocyte. In this review, we outline how certain effector proteins contribute to parasite survival, virulence, and immune evasion. We also highlight how parasite proteins destined for export are recognised at the endoplasmic reticulum to facilitate entry into the export pathway and how the effector proteins are able to transverse the bounding parasitophorous vaculoar membrane via the Plasmodium translocon of exported proteins to gain access to the host cell. Some of the gaps in our understanding of the export pathway are also presented. Finally, we examine the degree of conservation of some of the key components of the Plasmodium export pathway in closely related apicomplexan parasites, which may provide insight into how the diverse apicomplexan parasites have adapted to survival pressures encountered within their respective host cells.

show abstract

“…Rosetting is not only mediated by PfEMP1. The surface variant proteins subtelomeric variant open reading frame (STEVOR) and repetitive interspersed repeats (RIFIN), can also bind to uninfected erythrocytes [35]. Rosettes have been linked to all presentations of SM in African children [36].…”

Section: P Falciparum and Severe Malaria: Cytoadherence And Parasitementioning

confidence: 99%

New insights into microvascular injury to inform enhanced diagnostics and therapeutics for severe malaria

Erice

Kain

2019

Virulence

View full text Add to dashboard Cite

Severe malaria (SM) has high mortality and morbidity rates despite treatment with potent antimalarials. Disease onset and outcome is dependent upon both parasite and host factors. Infected erythrocytes bind to host endothelium contributing to microvascular occlusion and dysregulated inflammatory and immune host responses, resulting in endothelial activation and microvascular damage. This review focuses on the mechanisms of host endothelial and microvascular injury. Only a small percentage of malaria infections (≤1%) progress to SM. Early recognition and treatment of SM can improve outcome, but we lack triage tools to identify SM early in the course of infection. Current point-of-care pathogen-based rapid diagnostic tests do not address this critical barrier. Immune and endothelial activation have been implicated in the pathobiology of SM. We hypothesize that measuring circulating mediators of these pathways at first clinical presentation will enable early triage and treatment of SM. Moreover, that host-based interventions that modulate these pathways will stabilize the microvasculature and improve clinical outcome over that of antimalarial therapy alone. ARTICLE HISTORY

show abstract

Three Is a Crowd – New Insights into Rosetting in Plasmodium falciparum

Cited by 40 publications

References 109 publications

A new heparan sulfate from the mollusk Nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of Plasmodium falciparum

A new heparan sulfate from the mollusk Nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of Plasmodium falciparum

Illuminating how malaria parasites export proteins into host erythrocytes

New insights into microvascular injury to inform enhanced diagnostics and therapeutics for severe malaria

Contact Info

Product

Resources

About