Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD).
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Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD). / Ajonina-Ekoti, Irene; Ndjonka, Dieudonne; Tanyi, Manchang Kingsley; Wilbertz, Meike; Younis, Abuelhassan Elshazly; Boursou, Djafsia; Kurosinski, Marc Andre; Eberle, Raphael; Lüersen, Kai; Perbandt, Markus; Breloer, Minka; Brattig, Norbert W; Liebau, Eva.
in: ACTA TROP, Jahrgang 124, Nr. 1, 1, 2012, S. 15-26.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD).
AU - Ajonina-Ekoti, Irene
AU - Ndjonka, Dieudonne
AU - Tanyi, Manchang Kingsley
AU - Wilbertz, Meike
AU - Younis, Abuelhassan Elshazly
AU - Boursou, Djafsia
AU - Kurosinski, Marc Andre
AU - Eberle, Raphael
AU - Lüersen, Kai
AU - Perbandt, Markus
AU - Breloer, Minka
AU - Brattig, Norbert W
AU - Liebau, Eva
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Adult
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred BALB C
KW - Amino Acid Substitution
KW - Protein Conformation
KW - Protein Multimerization
KW - Mutagenesis, Site-Directed
KW - Caenorhabditis elegans
KW - Recombinant Proteins/genetics/isolation & purification/metabolism
KW - Cross Reactions
KW - Immunoglobulin G/blood
KW - Immunoglobulin M/blood
KW - Antibodies, Helminth/blood
KW - Catalytic Domain
KW - Filarioidea
KW - Mutant Proteins/genetics/isolation & purification/metabolism
KW - Nematoda
KW - Onchocerca
KW - Onchocerca volvulus/enzymology/genetics/immunology
KW - Onchocerciasis/immunology/parasitology/pathology
KW - Protein Sorting Signals
KW - Sigmodontinae
KW - Superoxide Dismutase/genetics/immunology/isolation & purification/metabolism
KW - Adult
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred BALB C
KW - Amino Acid Substitution
KW - Protein Conformation
KW - Protein Multimerization
KW - Mutagenesis, Site-Directed
KW - Caenorhabditis elegans
KW - Recombinant Proteins/genetics/isolation & purification/metabolism
KW - Cross Reactions
KW - Immunoglobulin G/blood
KW - Immunoglobulin M/blood
KW - Antibodies, Helminth/blood
KW - Catalytic Domain
KW - Filarioidea
KW - Mutant Proteins/genetics/isolation & purification/metabolism
KW - Nematoda
KW - Onchocerca
KW - Onchocerca volvulus/enzymology/genetics/immunology
KW - Onchocerciasis/immunology/parasitology/pathology
KW - Protein Sorting Signals
KW - Sigmodontinae
KW - Superoxide Dismutase/genetics/immunology/isolation & purification/metabolism
M3 - SCORING: Journal article
VL - 124
SP - 15
EP - 26
JO - ACTA TROP
JF - ACTA TROP
SN - 0001-706X
IS - 1
M1 - 1
ER -