LymphedemaV1, PubMed, Curation, bibRecord, 001649

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.

Identifieur interne : 001649 ( PubMed/Curation ); précédent : 001648; suivant : 001650

The 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 [ 1553-7374 ] ; 2014.

RBID : pubmed:24586152

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 Brugia malayi 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 B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60-70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4⁺ 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 B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections.

DOI: 10.1371/journal.ppat.1003930
PubMed: 24586152

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<front><div type="abstract" xml:lang="en">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 Brugia malayi 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 B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60-70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4⁺ 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 B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections.</div>
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<Abstract><AbstractText>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 Brugia malayi 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 B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60-70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4⁺ 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 B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections.</AbstractText>
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<Chemical><RegistryNumber>EC 5.3.1.1</RegistryNumber>
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</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000909" MajorTopicYN="N">Antibodies, Helminth</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057134" MajorTopicYN="N">Antibodies, Neutralizing</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015153" MajorTopicYN="N">Blotting, Western</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017178" MajorTopicYN="N">Brugia malayi</DescriptorName>
<QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000472" MajorTopicYN="Y">pathogenicity</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004605" MajorTopicYN="N">Elephantiasis, Filarial</DescriptorName>
<QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004797" MajorTopicYN="N">Enzyme-Linked Immunosorbent Assay</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005434" MajorTopicYN="N">Flow Cytometry</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005849" MajorTopicYN="N">Gerbillinae</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008842" MajorTopicYN="Y">Microfilariae</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014305" MajorTopicYN="N">Triose-Phosphate Isomerase</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<OtherID Source="NLM">PMC3937304</OtherID>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2013</Year>
<Month>07</Month>
<Day>29</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2014</Year>
<Month>01</Month>
<Day>02</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2014</Year>
<Month>3</Month>
<Day>4</Day>
<Hour>6</Hour>
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<PubMedPubDate PubStatus="pubmed"><Year>2014</Year>
<Month>3</Month>
<Day>4</Day>
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<PubMedPubDate PubStatus="medline"><Year>2014</Year>
<Month>10</Month>
<Day>4</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PublicationStatus>epublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">24586152</ArticleId>
<ArticleId IdType="doi">10.1371/journal.ppat.1003930</ArticleId>
<ArticleId IdType="pii">PPATHOGENS-D-13-01978</ArticleId>
<ArticleId IdType="pmc">PMC3937304</ArticleId>
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   |texte=   The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.
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The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo.

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