The Secreted Triose Phosphate Isomerase of Brugia malayi Is Required to Sustain Microfilaria Production In Vivo
Identifieur interne : 002436 ( Main/Exploration ); précédent : 002435; suivant : 002437The Secreted Triose Phosphate Isomerase of Brugia malayi Is Required to Sustain Microfilaria Production In Vivo
Auteurs : James P. Hewitson [Royaume-Uni] ; Dominik Rückerl [Royaume-Uni] ; Yvonne Harcus [Royaume-Uni] ; Janice Murray [Royaume-Uni] ; Lauren M. Webb [Royaume-Uni] ; Simon A. Babayan [Royaume-Uni] ; Judith E. Allen [Royaume-Uni] ; Agnes Kurniawan [Indonésie] ; Rick M. Maizels [Royaume-Uni]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antihelminthe (immunologie), Anticorps neutralisants (immunologie), Brugia malayi (enzymologie), Brugia malayi (immunologie), Brugia malayi (pathogénicité), Cytométrie en flux, Filariose lymphatique (enzymologie), Filariose lymphatique (immunologie), Gerbillinae, Humains, Immunohistochimie, Microfilaria, Souris, Souris de lignée BALB C, Technique de Western, Test ELISA, Triose phosphate isomerase (métabolisme).
- MESH :
- enzymologie : Brugia malayi, Filariose lymphatique.
- immunologie : Anticorps antihelminthe, Anticorps neutralisants, Brugia malayi, Filariose lymphatique.
- métabolisme : Triose phosphate isomerase.
- pathogénicité : Brugia malayi.
- Animaux, Cytométrie en flux, Gerbillinae, Humains, Immunohistochimie, Microfilaria, Souris, Souris de lignée BALB C, Technique de Western, Test ELISA.
English descriptors
- KwdEn :
- Animals, Antibodies, Helminth (immunology), Antibodies, Neutralizing (immunology), Blotting, Western, Brugia malayi (enzymology), Brugia malayi (immunology), Brugia malayi (pathogenicity), Elephantiasis, Filarial (enzymology), Elephantiasis, Filarial (immunology), Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Gerbillinae, Humans, Immunohistochemistry, Mice, Mice, Inbred BALB C, Microfilariae, Triose-Phosphate Isomerase (metabolism).
- MESH :
- chemical , immunology : Antibodies, Helminth, Antibodies, Neutralizing.
- enzymology : Brugia malayi, Elephantiasis, Filarial.
- immunology : Brugia malayi, Elephantiasis, Filarial.
- chemical , metabolism : Triose-Phosphate Isomerase.
- pathogenicity : Brugia malayi.
- Animals, Blotting, Western, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Gerbillinae, Humans, Immunohistochemistry, Mice, Mice, Inbred BALB C, Microfilariae.
Abstract
Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult
Url:
DOI: 10.1371/journal.ppat.1003930
PubMed: 24586152
PubMed Central: 3937304
Affiliations:
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Hewitson</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Ruckerl, Dominik" sort="Ruckerl, Dominik" uniqKey="Ruckerl D" first="Dominik" last="Rückerl">Dominik Rückerl</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Harcus, Yvonne" sort="Harcus, Yvonne" uniqKey="Harcus Y" first="Yvonne" last="Harcus">Yvonne Harcus</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Murray, Janice" sort="Murray, Janice" uniqKey="Murray J" first="Janice" last="Murray">Janice Murray</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Webb, Lauren M" sort="Webb, Lauren M" uniqKey="Webb L" first="Lauren M." last="Webb">Lauren M. Webb</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Babayan, Simon A" sort="Babayan, Simon A" uniqKey="Babayan S" first="Simon A." last="Babayan">Simon A. Babayan</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Allen, Judith E" sort="Allen, Judith E" uniqKey="Allen J" first="Judith E." last="Allen">Judith E. Allen</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Kurniawan, Agnes" sort="Kurniawan, Agnes" uniqKey="Kurniawan A" first="Agnes" last="Kurniawan">Agnes Kurniawan</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Parasitology, University of Indonesia, Jakarta, Indonesia</addr-line></nlm:aff><country xml:lang="fr">Indonésie</country><wicri:regionArea>Department of Parasitology, University of Indonesia, Jakarta</wicri:regionArea><wicri:noRegion>Jakarta</wicri:noRegion></affiliation></author><author><name sortKey="Maizels, Rick M" sort="Maizels, Rick M" uniqKey="Maizels R" first="Rick M." last="Maizels">Rick M. Maizels</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Helminth (immunology)</term><term>Antibodies, Neutralizing (immunology)</term><term>Blotting, Western</term><term>Brugia malayi (enzymology)</term><term>Brugia malayi (immunology)</term><term>Brugia malayi (pathogenicity)</term><term>Elephantiasis, Filarial (enzymology)</term><term>Elephantiasis, Filarial (immunology)</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Flow Cytometry</term><term>Gerbillinae</term><term>Humans</term><term>Immunohistochemistry</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Microfilariae</term><term>Triose-Phosphate Isomerase (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antihelminthe (immunologie)</term><term>Anticorps neutralisants (immunologie)</term><term>Brugia malayi (enzymologie)</term><term>Brugia malayi (immunologie)</term><term>Brugia malayi (pathogénicité)</term><term>Cytométrie en flux</term><term>Filariose lymphatique (enzymologie)</term><term>Filariose lymphatique (immunologie)</term><term>Gerbillinae</term><term>Humains</term><term>Immunohistochimie</term><term>Microfilaria</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Technique de Western</term><term>Test ELISA</term><term>Triose phosphate isomerase (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Helminth</term><term>Antibodies, Neutralizing</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Brugia malayi</term><term>Filariose lymphatique</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Brugia malayi</term><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antihelminthe</term><term>Anticorps neutralisants</term><term>Brugia malayi</term><term>Filariose lymphatique</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Brugia malayi</term><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Triose-Phosphate Isomerase</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Triose phosphate isomerase</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Brugia malayi</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Brugia malayi</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blotting, Western</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Flow Cytometry</term><term>Gerbillinae</term><term>Humans</term><term>Immunohistochemistry</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Microfilariae</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cytométrie en flux</term><term>Gerbillinae</term><term>Humains</term><term>Immunohistochimie</term><term>Microfilaria</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Technique de Western</term><term>Test ELISA</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult <italic>Brugia malay</italic>i is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with <italic>B. malayi</italic> TPI, or mice with the homologous protein from the rodent filaria <italic>Litomosoides sigmodontis</italic>, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult <italic>B. malayi</italic> resulted in 60–70% reductions in microfilarial levels <italic>in vivo</italic> and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4<sup>+</sup> T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of <italic>B. malayi</italic> filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Babu, S" uniqKey="Babu S">S Babu</name></author><author><name sortKey="Nutman, Tb" uniqKey="Nutman T">TB Nutman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gregory, Wf" uniqKey="Gregory W">WF Gregory</name></author><author><name sortKey="Atmadja, Ak" uniqKey="Atmadja A">AK Atmadja</name></author><author><name sortKey="Allen, Je" uniqKey="Allen J">JE Allen</name></author><author><name sortKey="Maizels, Rm" uniqKey="Maizels R">RM Maizels</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Babayan, Sa" uniqKey="Babayan S">SA Babayan</name></author><author><name 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Rossner</name></author><author><name sortKey="Koch, F" uniqKey="Koch F">F Koch</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Indonésie</li><li>Royaume-Uni</li></country><region><li>Écosse</li></region><settlement><li>Édimbourg</li></settlement><orgName><li>Université d'Édimbourg</li></orgName></list><tree><country name="Royaume-Uni"><region name="Écosse"><name sortKey="Hewitson, James P" sort="Hewitson, James P" uniqKey="Hewitson J" first="James P." last="Hewitson">James P. Hewitson</name></region><name sortKey="Allen, Judith E" sort="Allen, Judith E" uniqKey="Allen J" first="Judith E." last="Allen">Judith E. Allen</name><name sortKey="Babayan, Simon A" sort="Babayan, Simon A" uniqKey="Babayan S" first="Simon A." last="Babayan">Simon A. Babayan</name><name sortKey="Harcus, Yvonne" sort="Harcus, Yvonne" uniqKey="Harcus Y" first="Yvonne" last="Harcus">Yvonne Harcus</name><name sortKey="Maizels, Rick M" sort="Maizels, Rick M" uniqKey="Maizels R" first="Rick M." last="Maizels">Rick M. Maizels</name><name sortKey="Murray, Janice" sort="Murray, Janice" uniqKey="Murray J" first="Janice" last="Murray">Janice Murray</name><name sortKey="Ruckerl, Dominik" sort="Ruckerl, Dominik" uniqKey="Ruckerl D" first="Dominik" last="Rückerl">Dominik Rückerl</name><name sortKey="Webb, Lauren M" sort="Webb, Lauren M" uniqKey="Webb L" first="Lauren M." last="Webb">Lauren M. Webb</name></country><country name="Indonésie"><noRegion><name sortKey="Kurniawan, Agnes" sort="Kurniawan, Agnes" uniqKey="Kurniawan A" first="Agnes" last="Kurniawan">Agnes Kurniawan</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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