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ABSTRACT: Haemonchus contortus is an economically important gastrointestinal parasite of domestic animals. The parasite secretes calreticulin (CalR), a Ca(++) binding protein which modulates the host immune response. One way by which this protein acts is by inhibiting the classical complement pathway by binding to complement C1q protein. Understanding CalR-C1q interaction is important to develop methods to enhance host immune response. In this study, we have mapped the regions in the N-domain of CalR that facilitates C1q binding by generating small recombinant fragments of the domain and using synthetic peptides. In addition to already identified C1q binding motifs in human CalR, two additional sites in the N-domain of H. contortus were revealed with the following sequences-GKYYDDAKRD and the AKFPKKFT. The significance of multiple C1q binding motifs in CalR is discussed in relation to host-parasite interactions.
Molecular and Biochemical Parasitology 08/2009; 166(1):42-6. · 2.55 Impact Factor
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ABSTRACT: Calreticulin (CalR), a Ca(2+) binding multifunctional protein, is secreted by the parasitic nematode Haemonchus contortus. We have earlier observed binding of this protein to a 24-kDa polypeptide (p24) present in an enriched preparation of prothrombin. In the present study, the identity of p24 was established as a C-reactive protein (CRP) by several criteria. CalR binding to CRP is an elegant strategy devised by the parasite to survive in the host. The secreted CalR may achieve this either by limiting the free concentration of CRP, which has antiparasite activity or inhibit the activation of the classical complement pathway triggered on binding of CRP to C1q protein. CalR binding to CRP would also ensure a check on the procoagulant activity of the CRP enabling parasite to feed on the host blood. Thus, targeting CalR could be a novel strategy to tackle this parasite, which has developed resistance to many anthelmintics.
Parasite Immunology 05/2008; 30(6-7):371-4. · 2.60 Impact Factor
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ABSTRACT: A 66 kDa adult Haemonchus contortus excretory/secretory (E/S) antigen was identified in Western blot by reaction with sera from the infected goats. The protein was purified from the adult worm extract and E/S products by anion exchange and ConA-Sepharose chromatography. The purified protein inhibited monocyte function in vitro as judged by decreased production of hydrogen peroxide and nitric oxide in the culture medium. The protein also caused proliferation of peripheral blood mononuclear cells. The absence of protein in the free living L3 larvae suggests that the expression of this protein coincides with the adaptation to the parasitic life. A correlation of antibody titre and worm burden was observed in the infected goats with higher antibody levels in high worm burdened animals. Anti-protein antibody caused loss of adult worm motility in vitro resulting in the death of the parasite. The fact that the protein is recognized by the host together with in vitro killing of adult parasites by antibodies makes this protein a promising candidate for vaccination trial.
Veterinary Parasitology 07/2006; 138(3-4):291-300. · 2.58 Impact Factor
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Vet Parasitol. 01/2006; 138:291-300.
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ABSTRACT: Haemonchus contortus is an economically important gastrointestinal parasite of domestic animals. The parasite secretes calreticulin (CalR), a Ca++ binding protein which modulates the host immune response. One way by which this protein acts is by inhibiting the classical complement pathway by binding to complement C1q protein. Understanding CalR–C1q interaction is important to develop methods to enhance host immune response. In this study, we have mapped the regions in the N-domain of CalR that facilitates C1q binding by generating small recombinant fragments of the domain and using synthetic peptides. In addition to already identified C1q binding motifs in human CalR, two additional sites in the N-domain of H. contortus were revealed with the following sequences—GKYYDDAKRD and the AKFPKKFT. The significance of multiple C1q binding motifs in CalR is discussed in relation to host–parasite interactions.
Molecular and Biochemical Parasitology.
