Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD).

Irene Ajonina-Ekoti; Dieudonne Ndjonka; Manchang Kingsley Tanyi; Meike Wilbertz; Abuelhassan Elshazly Younis; Djafsia Boursou; Marc Andre Kurosinski; Raphael Eberle; Kai Lüersen; Markus Perbandt; Minka Breloer; Norbert W Brattig; Eva Liebau

Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD).

Standard

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, Vol. 124, No. 1, 1, 2012, p. 15-26.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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, E 2012, 'Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD).', ACTA TROP, vol. 124, no. 1, 1, pp. 15-26. <http://www.ncbi.nlm.nih.gov/pubmed/22677600?dopt=Citation>

APA

Ajonina-Ekoti, I., Ndjonka, D., Tanyi, M. K., Wilbertz, M., Younis, A. E., Boursou, D., Kurosinski, M. A., Eberle, R., Lüersen, K., Perbandt, M., Breloer, M., Brattig, N. W., & Liebau, E. (2012). Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD). ACTA TROP, 124(1), 15-26. [1]. http://www.ncbi.nlm.nih.gov/pubmed/22677600?dopt=Citation

Vancouver

Ajonina-Ekoti I, Ndjonka D, Tanyi MK, Wilbertz M, Younis AE, Boursou D et al. Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD). ACTA TROP. 2012;124(1):15-26. 1.

Bibtex

@article{eae00272e9654eaba930d24bf568fe94,

title = "Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC-SOD).",

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.",

keywords = "Adult, Animals, Humans, Male, Female, Middle Aged, Disease Models, Animal, Mice, Mice, Inbred BALB C, Amino Acid Substitution, Protein Conformation, Protein Multimerization, Mutagenesis, Site-Directed, Caenorhabditis elegans, Recombinant Proteins/genetics/isolation & purification/metabolism, Cross Reactions, Immunoglobulin G/blood, Immunoglobulin M/blood, Antibodies, Helminth/blood, Catalytic Domain, Filarioidea, Mutant Proteins/genetics/isolation & purification/metabolism, Nematoda, Onchocerca, Onchocerca volvulus/*enzymology/genetics/immunology, Onchocerciasis/immunology/parasitology/pathology, Protein Sorting Signals, Sigmodontinae, Superoxide Dismutase/genetics/immunology/isolation & purification/*metabolism, Adult, Animals, Humans, Male, Female, Middle Aged, Disease Models, Animal, Mice, Mice, Inbred BALB C, Amino Acid Substitution, Protein Conformation, Protein Multimerization, Mutagenesis, Site-Directed, Caenorhabditis elegans, Recombinant Proteins/genetics/isolation & purification/metabolism, Cross Reactions, Immunoglobulin G/blood, Immunoglobulin M/blood, Antibodies, Helminth/blood, Catalytic Domain, Filarioidea, Mutant Proteins/genetics/isolation & purification/metabolism, Nematoda, Onchocerca, Onchocerca volvulus/*enzymology/genetics/immunology, Onchocerciasis/immunology/parasitology/pathology, Protein Sorting Signals, Sigmodontinae, Superoxide Dismutase/genetics/immunology/isolation & purification/*metabolism",

author = "Irene Ajonina-Ekoti and Dieudonne Ndjonka and Tanyi, {Manchang Kingsley} and Meike Wilbertz and Younis, {Abuelhassan Elshazly} and Djafsia Boursou and Kurosinski, {Marc Andre} and Raphael Eberle and Kai L{\"u}ersen and Markus Perbandt and Minka Breloer and Brattig, {Norbert W} and Eva Liebau",

year = "2012",

language = "English",

volume = "124",

pages = "15--26",

journal = "ACTA TROP",

issn = "0001-706X",

publisher = "Elsevier",

number = "1",

}

RIS

TY - JOUR

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