Abstract:
:Onchocerca volvulus is a human pathogenic filarial nematode causing chronic onchocerciasis, a disease characterized by chronic skin and eye lesions. Despite attempts to control this infection from many perspectives, it still remains a threat to public health because of adverse effects of available drugs and recent reports of drug resistance. Under control of an intact immune system, O. volvulus survives for a long time in the host by employing a variety of strategies including the utility of antioxidant enzymes. In the present study, we focus on the extracellular superoxide dismutase from O. volvulus (OvEC-SOD) found in the excretory/secretory products of adult worms. Contrary to previous studies, the OvEC-SOD was found to have a 19 amino acid long signal peptide that is cleaved off during the process of maturation. To validate this result, we designed a novel method based on Caenorhabditis elegans cup5(ar465) mutants to specifically evaluate signal peptide-mediated secretion of nematodal proteins. Following purification, the recombinant OvEC-SOD was active as a dimer. Site-directed mutagenesis of the three cysteines present in the OvEC-SOD shows that enzyme activity is markedly reduced in the Cys-192 mutant. A homology model of the OvEC-SOD underlines the importance of Cys-192 for the stabilization of the adjacent active site channel. The generation of a humoral immune response to secretory OvEC-SOD was indicated by demonstrating IgG reactivity in sera from patients infected with O. volvulus while the cross-reactivity of IgG in plasma samples from cows, infected with the most closely related parasite Onchocerca ochengi, occurred only marginally. High IgG1 and IgM titres were recorded in sera from mice infected with the filaria Litomosoides sigmodontis, however, low or no cellular proliferative responses were observed. Thus, the present data suggest that secretory OvEC-SOD is a target of the humoral immune response in human onchocerciasis and induced strongest IgG responses in hyperreactive onchocerciasis. Furthermore, humoral response during murine infection induced SOD-specific IgG that cross-reacted with OvEC-SOD.
journal_name
Acta Tropjournal_title
Acta tropicaauthors
Ajonina-Ekoti I,Ndjonka D,Tanyi MK,Wilbertz M,Younis AE,Boursou D,Kurosinski MA,Eberle R,Lüersen K,Perbandt M,Breloer M,Brattig NW,Liebau Edoi
10.1016/j.actatropica.2012.05.013subject
Has Abstractpub_date
2012-10-01 00:00:00pages
15-26issue
1eissn
0001-706Xissn
1873-6254pii
S0001-706X(12)00223-9journal_volume
124pub_type
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