Protozoan parasites including Plasmodia, Leishmania, Trypanosoma, Entamoeba, Trichomonas and others cause diseases in humans and domestic livestock having far-reaching socio-economic implications. They show remarkable propensity to survive within hostile environments encountered during their life cycle, and the identification of molecules that enable them to survive in such milieu is a subject of intense research. Currently available knowledge of the parasite cell surface architecture and biochemistry indicates that sialic acid and its principle derivatives are major components of the glycocalyx and assist the parasite to interact with its external environment through functions ranging from parasite survival, infectivity and host-cell recognition. This review highlights the present state of knowledge with regard to parasite sialobiology with an emphasis on its mode(s) of acquisition and their emerging biological roles, notably as an anti-recognition molecule thereby aiding the pathogen to evade host defense mechanisms.
Human C-reactive protein (CRP) is a clinically important classical acute phase protein. Although CRP has been reported to bind with many nucleated cells, the direct binding of CRP to erythrocytes in diseases remains largely unexplored. The main focus of the present study was to investigate the binding of disease-specific CRP to erythrocytes of same patients. Distinct molecular variant of disease-specific CRP was affinity purified from sera of malaria patients (CRP(Mal)). This CRP showed strong binding with malaria erythrocytes (RBC(Mal)) as confirmed by flow cytometric analysis (FACS), enzyme-linked immunosorbent assays (ELISA), and radio binding assays. Calcium and phosphoryl choline (PC) were found to be essential for this interaction. A 2.3-fold increased binding of induced CRP to RBC(Mal) as compared to normal erythrocytes (RBC(N)) confirmed disease-specificity. Preincubation of RBC(Mal) with unconjugated CRP showed 3-5 fold inhibition. The association constant of CRP and RBC(Mal) was 4.7 x 10(6) cpm/microg with the corresponding number of receptors/cell being 4.3 x 10(5). The effector function of CRP(Mal) has been demonstrated by its potency to activate the complement pathway. An optimal dose of 10 microg/ml of CRP induced three-fold higher hemolysis of patient erythrocytes as compared to RBC(N). These studies provide direct evidence for an important phagocytic functional interaction of this acute-phase protein by triggering the CRP-complement pathway after the binding of CRP(Mal) with RBC(Mal). Hemolysis as triggered by this pathway may be one of the causative factors of anemia, a common clinical manifestation of this disease.
Anti-O-AcSGs were identified as an important source of CP activation under normal physiological conditions, suggesting that they play a role in conferring host protection against parasite infection.
Although the existence of O -acetylated sialic acids is well known, it is only in recent years that steady refinement of analytical techniques have enabled detailed mapping of their structural diversity [1]. Fluorimetric analysis of peripheral blood mononuclear cells (PBMC) of patients with Visceral Leishmaniasis (VL) showed six fold increase in the percentage of surface 9-O-acetylated sialoglycoconjugates (9-O-AcSGs) as compared to normal human donors. Using Achatinin-H, a 9-O-acetyl sialic acid- binding lectin, an enhanced presence of 9-O-AcSGs in an alpha2 --> 6 linkage was demonstrated by flow cytometry; abolition of its binding by pretreatment with a recombinant 9-O-acetylesterase corroborated the presence of this glycotope. Western blotting of PBMC from VL patients indicated the presence of five O-acetylated sialoglycans corresponding to 144, 65, 56, 36 and 19 kDa as compared to 144 and 36 kDa in normal individuals. Taken together our data indicates that during active disease, there is an overexpression of 9AcSGs on the surface of PBMC of VL patients, thus opening up new research avenues wherein the expression of this biomarker could be exploited to monitor the clinical status of VL patients.
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