New Inflammation-Related Biomarkers during Malaria Infection

Fikregabrail Aberra Kassa,Momar Ndao,Marina Tiemi Shio,Babacar Faye,Martin Olivier,Marie-Josée Bellemare,Gordon Langsley

doi:10.1371/journal.pone.0026495

Fikregabrail Aberra Kassa, Momar Ndao + Show 5 more

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https://doi.org/10.1371/journal.pone.0026495

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Abstract

Malaria is one of the most prevalent infectious diseases worldwide with more than 250 million cases and one million deaths each year. One of the well-characterized malarial-related molecules is hemozoin (HZ), which is a dark-brown crystal formed by the parasite and released into the host during the burst of infected red blood cells. HZ has a stimulatory effect on the host immune system such as its ability to induce pro-inflammatory mediators responsible for some of the malaria related clinical symptoms such as fever. However, the host serum proteins interacting with malarial HZ as well as how this interaction modifies its recognition by phagocytes remained elusive. In the actual study, using proteomic liquid chromatographic mass spectrometry (LC-MS/MS) and immunochemical approaches, we compared the serum protein profiles of malaria patients and healthy individuals. Particularly, we utilized the malarial HZ itself to capture serum proteins capable to bind to HZ, enabling us to identify several proteins such as apolipoprotein E (ApoE), serum amyloid A (SAA), gelsolin, complement factor H and fibrinogen that were found to differ among healthy and malaria individual. Of particular interest is LPS binding protein (LBP), which is reported herein for the first time in the context of malaria. LBP is usually produced during innate inflammatory response to gram-negative bacterial infections. The exact role of these biomarkers and acute phase responses in malaria in general and HZ in particular remains to be investigated. The identification of these inflammation-related biomarkers in malaria paves the way to potentially utilize them as diagnostic and therapeutic targets.

Highlights

Malaria is one of the major public health problems worldwide affecting more than 250 million people causing over one million deaths each year
In order to visualize the profile of proteins capable to bind to HZ, a synthetic HZ was incubated with serum samples from healthy individuals and malaria patients, and the protein-coated HZ crystal was run onto gel followed by silver staining
serum amyloid A (SAA) along with C reactive protein (CRP) has been proven to be valuable in assessing the severity of malaria and as a prognostic tool in following response to treatments [20]

Summary

Introduction

Malaria is one of the major public health problems worldwide affecting more than 250 million people causing over one million deaths each year. Caused by the Plasmodium parasite and transmitted through the bite of an infected female Anopheles mosquito, malaria still remains to be a major public health burden to the developing nations [1]. Severe P. falciparum mediated malaria, is characterized by cerebral malaria, severe anemia, renal failure, metabolic acidosis, and hyperparasitemia, where more than 5% of the red blood cells (RBC) are infected by the parasites [2]. Severe malaria, which is a complex multi-system disorder, has clinical similarities with sepsis. Metabolic acidosis, which is the excessive acidity in the blood and tissue fluids, is observed in severe malaria patients [3]

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