Identification of Host‐Response in Cerebral Malaria Patients Using Quantitative Proteomic Analysis

Kumar, Manish; Varun, Chakrakodi N.; Dey, Gourav; Ravikumar, Raju; Mahadevan, Anita; Shankar, Susarla Krishna; Prasad, T. S. Keshava

doi:10.1002/prca.201600187

Cited by 14 publications

(10 citation statements)

References 50 publications

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“…Platelet activation and thrombosis may precede leukocyte infiltration (88). Moreover, recent proteomic studies performed on postmortem brain tissue obtained from CM patients revealed that proteins involved in platelet activation and coagulation were upregulated (93). Thus, platelets and leukocytes (as well as platelet-leukocyte aggregates) are associated with CM.…”

Section: Malariamentioning

confidence: 99%

The Era of Thromboinflammation: Platelets Are Dynamic Sensors and Effector Cells During Infectious Diseases

2019

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Platelets are anucleate cells produced by megakaryocytes. In recent years, a robust body of literature supports the evolving role of platelets as key sentinel and effector cells in infectious diseases, especially critical in bridging hemostatic, inflammatory, and immune continuums. Upon intravascular pathogen invasion, platelets can directly sense viral, parasitic, and bacterial infections through pattern recognition receptors and integrin receptors or pathogen: immunoglobulin complexes through Fc and complement receptors—although our understanding of these interactions remains incomplete. Constantly scanning for areas of injury or inflammation as they circulate in the vasculature, platelets also indirectly respond to pathogen invasion through interactions with leukocytes and the endothelium. Following antigen recognition, platelets often become activated. Through a diverse repertoire of mechanisms, activated platelets can directly sequester or kill pathogens, or facilitate pathogen clearance by activating macrophages and neutrophils, promoting neutrophil extracellular traps (NETs) formation, forming platelet aggregates and microthrombi. At times, however, platelet activation may also be injurious to the host, exacerbating inflammation and promoting endothelial damage and thrombosis. There are many gaps in our understandings of the role of platelets in infectious diseases. However, with the emergence of advanced technologies, our knowledge is increasing. In the current review, we mainly discuss these evolving roles of platelets under four different infectious pathogen infections, of which are dengue, malaria, Esterichia coli (E. coli) and staphylococcus aureus S. aureus, highlighting the complex interplay of these processes with hemostatic and thrombotic pathways.

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Section: Malariamentioning

confidence: 99%

The Era of Thromboinflammation: Platelets Are Dynamic Sensors and Effector Cells During Infectious Diseases

2019

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“…In recent years, plasma/serum proteomics studies have contributed substantially to elucidate the complex pathogenesis of malaria and other infectious diseases 17,18 . Intriguingly, several studies from our and other research groups have defined promising panels of plasma and serum markers in falciparum [19][20][21][22][23][24] and vivax 19,25,26 malaria. A considerable amount of further research is required to understand the complex pathophysiology of severe malaria [27][28][29] .…”

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confidence: 99%

Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity

Kumar

Aggarwal

et al. 2020

Commun Biol

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Management of severe malaria remains a critical global challenge. In this study, using a multiplexed quantitative proteomics pipeline we systematically investigated the plasma proteome alterations in non-severe and severe malaria patients. We identified a few parasite proteins in severe malaria patients, which could be promising from a diagnostic perspective. Further, from host proteome analysis we observed substantial modulations in many crucial physiological pathways, including lipid metabolism, cytokine signaling, complement, and coagulation cascades in severe malaria. We propose that severe manifestations of malaria are possibly underpinned by modulations of the host physiology and defense machinery, which is evidently reflected in the plasma proteome alterations. Importantly, we identified multiple blood markers that can effectively define different complications of severe falciparum malaria, including cerebral syndromes and severe anemia. The ability of our identified blood markers to distinguish different severe complications of malaria may aid in developing new clinical tests for monitoring malaria severity.

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“…In accordance with this, a recent proteomic analysis, showed that there was an increase in proteins in biological pathways involved in the innate immune response and complement system in CM patients [56]. Moreover, a pilot study looking at microarray data from a population from Mali with SM and UM showed that differential and increased expression of TLR and complement proteins was associated with disease severity [57].…”

Section: Coagulation and Inflammationmentioning

confidence: 60%

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

Erice

Kain

2019

Virulence

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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

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Identification of Host‐Response in Cerebral Malaria Patients Using Quantitative Proteomic Analysis

Cited by 14 publications

References 50 publications

The Era of Thromboinflammation: Platelets Are Dynamic Sensors and Effector Cells During Infectious Diseases

The Era of Thromboinflammation: Platelets Are Dynamic Sensors and Effector Cells During Infectious Diseases

Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity

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

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