Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria
Identifieur interne : 001377 ( Pmc/Curation ); précédent : 001376; suivant : 001378Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria
Auteurs : Dieudonnée Togbe [France] ; Paulo Loureiro De Sousa [France] ; Mathilde Fauconnier [France] ; Victorine Boissay [France] ; Lizette Fick [Afrique du Sud] ; Stefanie Scheu [Allemagne] ; Klaus Pfeffer [Allemagne] ; Robert Menard [France] ; Georges E. Grau [Australie] ; Bich-Thuy Doan [France] ; Jean Claude Beloeil [France] ; Laurent Renia [Australie, France] ; Anna M. Hansen [Australie] ; Helen J. Ball [Australie] ; Nicholas H. Hunt [Australie] ; Bernhard Ryffel [France] ; Valerie F. J. Quesniaux [France]Source :
- PLoS ONE [ 1932-6203 ] ; 2008.
Abstract
TNF-related lymphotoxin α (LTα) is essential for the development of
LTβR deficient mice did not develop the neurological signs seen in PbA induced ECM but died at three weeks with high parasitaemia and severe anemia like LTαβ deficient mice. Resistance of LTαβ or LTβR deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin+ CD8+ T cells, and their ICAM-1 expression were clearly attenuated in the brain of resistant mice. An essential contribution of LIGHT, another LTβR ligand, could be excluded, as LIGHT deficient mice rapidly succumbed to ECM.
LTβR expressed on radioresistant resident stromal, probably endothelial cells, rather than hematopoietic cells, are essential for the development of ECM, as assessed by hematopoietic reconstitution experiment. Therefore, the data suggest that both functional LTβR and TNFR2 signaling are required and non-redundant for the development of microvascular pathology resulting in fatal ECM.
Url:
DOI: 10.1371/journal.pone.0002608
PubMed: 18612394
PubMed Central: 2442868
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001517
Links to Exploration step
PMC:2442868Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria</title>
<author><name sortKey="Togbe, Dieudonnee" sort="Togbe, Dieudonnee" uniqKey="Togbe D" first="Dieudonnée" last="Togbe">Dieudonnée Togbe</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Loureiro De Sousa, Paulo" sort="Loureiro De Sousa, Paulo" uniqKey="Loureiro De Sousa P" first="Paulo" last="Loureiro De Sousa">Paulo Loureiro De Sousa</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>CNRS CBM (Centre de Biophysique Moléculaire), Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS CBM (Centre de Biophysique Moléculaire), Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fauconnier, Mathilde" sort="Fauconnier, Mathilde" uniqKey="Fauconnier M" first="Mathilde" last="Fauconnier">Mathilde Fauconnier</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Boissay, Victorine" sort="Boissay, Victorine" uniqKey="Boissay V" first="Victorine" last="Boissay">Victorine Boissay</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fick, Lizette" sort="Fick, Lizette" uniqKey="Fick L" first="Lizette" last="Fick">Lizette Fick</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa</addr-line>
</nlm:aff>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Institute of Infectious Disease and Molecular Medicine, Cape Town</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Scheu, Stefanie" sort="Scheu, Stefanie" uniqKey="Scheu S" first="Stefanie" last="Scheu">Stefanie Scheu</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>University of Duesseldorf, Duesseldorf, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University of Duesseldorf, Duesseldorf</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pfeffer, Klaus" sort="Pfeffer, Klaus" uniqKey="Pfeffer K" first="Klaus" last="Pfeffer">Klaus Pfeffer</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>University of Duesseldorf, Duesseldorf, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University of Duesseldorf, Duesseldorf</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Menard, Robert" sort="Menard, Robert" uniqKey="Menard R" first="Robert" last="Menard">Robert Menard</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Pasteur Institute Paris, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pasteur Institute Paris, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Grau, Georges E" sort="Grau, Georges E" uniqKey="Grau G" first="Georges E." last="Grau">Georges E. Grau</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Doan, Bich Thuy" sort="Doan, Bich Thuy" uniqKey="Doan B" first="Bich-Thuy" last="Doan">Bich-Thuy Doan</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>CNRS CBM (Centre de Biophysique Moléculaire), Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS CBM (Centre de Biophysique Moléculaire), Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Beloeil, Jean Claude" sort="Beloeil, Jean Claude" uniqKey="Beloeil J" first="Jean Claude" last="Beloeil">Jean Claude Beloeil</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>CNRS CBM (Centre de Biophysique Moléculaire), Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS CBM (Centre de Biophysique Moléculaire), Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Renia, Laurent" sort="Renia, Laurent" uniqKey="Renia L" first="Laurent" last="Renia">Laurent Renia</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Inserm, U567, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U567, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hansen, Anna M" sort="Hansen, Anna M" uniqKey="Hansen A" first="Anna M." last="Hansen">Anna M. Hansen</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ball, Helen J" sort="Ball, Helen J" uniqKey="Ball H" first="Helen J." last="Ball">Helen J. Ball</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hunt, Nicholas H" sort="Hunt, Nicholas H" uniqKey="Hunt N" first="Nicholas H." last="Hunt">Nicholas H. Hunt</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ryffel, Bernhard" sort="Ryffel, Bernhard" uniqKey="Ryffel B" first="Bernhard" last="Ryffel">Bernhard Ryffel</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Quesniaux, Valerie F J" sort="Quesniaux, Valerie F J" uniqKey="Quesniaux V" first="Valerie F. J." last="Quesniaux">Valerie F. J. Quesniaux</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">18612394</idno>
<idno type="pmc">2442868</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442868</idno>
<idno type="RBID">PMC:2442868</idno>
<idno type="doi">10.1371/journal.pone.0002608</idno>
<date when="2008">2008</date>
<idno type="wicri:Area/Pmc/Corpus">001517</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001517</idno>
<idno type="wicri:Area/Pmc/Curation">001377</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001377</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria</title>
<author><name sortKey="Togbe, Dieudonnee" sort="Togbe, Dieudonnee" uniqKey="Togbe D" first="Dieudonnée" last="Togbe">Dieudonnée Togbe</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Loureiro De Sousa, Paulo" sort="Loureiro De Sousa, Paulo" uniqKey="Loureiro De Sousa P" first="Paulo" last="Loureiro De Sousa">Paulo Loureiro De Sousa</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>CNRS CBM (Centre de Biophysique Moléculaire), Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS CBM (Centre de Biophysique Moléculaire), Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fauconnier, Mathilde" sort="Fauconnier, Mathilde" uniqKey="Fauconnier M" first="Mathilde" last="Fauconnier">Mathilde Fauconnier</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Boissay, Victorine" sort="Boissay, Victorine" uniqKey="Boissay V" first="Victorine" last="Boissay">Victorine Boissay</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fick, Lizette" sort="Fick, Lizette" uniqKey="Fick L" first="Lizette" last="Fick">Lizette Fick</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa</addr-line>
</nlm:aff>
<country xml:lang="fr">Afrique du Sud</country>
<wicri:regionArea>Institute of Infectious Disease and Molecular Medicine, Cape Town</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Scheu, Stefanie" sort="Scheu, Stefanie" uniqKey="Scheu S" first="Stefanie" last="Scheu">Stefanie Scheu</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>University of Duesseldorf, Duesseldorf, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University of Duesseldorf, Duesseldorf</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pfeffer, Klaus" sort="Pfeffer, Klaus" uniqKey="Pfeffer K" first="Klaus" last="Pfeffer">Klaus Pfeffer</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>University of Duesseldorf, Duesseldorf, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>University of Duesseldorf, Duesseldorf</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Menard, Robert" sort="Menard, Robert" uniqKey="Menard R" first="Robert" last="Menard">Robert Menard</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Pasteur Institute Paris, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pasteur Institute Paris, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Grau, Georges E" sort="Grau, Georges E" uniqKey="Grau G" first="Georges E." last="Grau">Georges E. Grau</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Doan, Bich Thuy" sort="Doan, Bich Thuy" uniqKey="Doan B" first="Bich-Thuy" last="Doan">Bich-Thuy Doan</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>CNRS CBM (Centre de Biophysique Moléculaire), Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS CBM (Centre de Biophysique Moléculaire), Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Beloeil, Jean Claude" sort="Beloeil, Jean Claude" uniqKey="Beloeil J" first="Jean Claude" last="Beloeil">Jean Claude Beloeil</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>CNRS CBM (Centre de Biophysique Moléculaire), Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS CBM (Centre de Biophysique Moléculaire), Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Renia, Laurent" sort="Renia, Laurent" uniqKey="Renia L" first="Laurent" last="Renia">Laurent Renia</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Inserm, U567, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U567, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hansen, Anna M" sort="Hansen, Anna M" uniqKey="Hansen A" first="Anna M." last="Hansen">Anna M. Hansen</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ball, Helen J" sort="Ball, Helen J" uniqKey="Ball H" first="Helen J." last="Ball">Helen J. Ball</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hunt, Nicholas H" sort="Hunt, Nicholas H" uniqKey="Hunt N" first="Nicholas H." last="Hunt">Nicholas H. Hunt</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Sydney, Department of Pathology, Camperdown</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ryffel, Bernhard" sort="Ryffel, Bernhard" uniqKey="Ryffel B" first="Bernhard" last="Ryffel">Bernhard Ryffel</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Quesniaux, Valerie F J" sort="Quesniaux, Valerie F J" uniqKey="Quesniaux V" first="Valerie F. J." last="Quesniaux">Valerie F. J. Quesniaux</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>TNF-related lymphotoxin α (LTα) is essential for the development of <italic>Plasmodium berghei</italic>
ANKA (PbA)-induced experimental cerebral malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a second arm of LTα-signaling essential for ECM development through LTβ-R, receptor of LTα1β2 heterotrimer.</p>
</sec>
<sec><title>Methodology/Principal Findings</title>
<p>LTβR deficient mice did not develop the neurological signs seen in PbA induced ECM but died at three weeks with high parasitaemia and severe anemia like LTαβ deficient mice. Resistance of LTαβ or LTβR deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin<sup>+</sup>
CD8<sup>+</sup>
T cells, and their ICAM-1 expression were clearly attenuated in the brain of resistant mice. An essential contribution of LIGHT, another LTβR ligand, could be excluded, as LIGHT deficient mice rapidly succumbed to ECM.</p>
</sec>
<sec><title>Conclusions/Significance</title>
<p>LTβR expressed on radioresistant resident stromal, probably endothelial cells, rather than hematopoietic cells, are essential for the development of ECM, as assessed by hematopoietic reconstitution experiment. Therefore, the data suggest that both functional LTβR and TNFR2 signaling are required and non-redundant for the development of microvascular pathology resulting in fatal ECM.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title>PLoS ONE</journal-title>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">18612394</article-id>
<article-id pub-id-type="pmc">2442868</article-id>
<article-id pub-id-type="publisher-id">08-PONE-RA-04095R1</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0002608</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline"><subject>Immunology/Immunity to Infections</subject>
<subject>Infectious Diseases/Protozoal Infections</subject>
<subject>Radiology and Medical Imaging/Magnetic Resonance Imaging</subject>
<subject>Radiology and Medical Imaging/Magnetic Resonance Imaging</subject>
</subj-group>
</article-categories>
<title-group><article-title>Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria</article-title>
<alt-title alt-title-type="running-head">LTbR in Cerebral Malaria</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Togbe</surname>
<given-names>Dieudonnée</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Loureiro de Sousa</surname>
<given-names>Paulo</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fauconnier</surname>
<given-names>Mathilde</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Boissay</surname>
<given-names>Victorine</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fick</surname>
<given-names>Lizette</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Scheu</surname>
<given-names>Stefanie</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pfeffer</surname>
<given-names>Klaus</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Menard</surname>
<given-names>Robert</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Grau</surname>
<given-names>Georges E.</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Doan</surname>
<given-names>Bich-Thuy</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Beloeil</surname>
<given-names>Jean Claude</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Renia</surname>
<given-names>Laurent</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
<xref ref-type="aff" rid="aff8"><sup>8</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hansen</surname>
<given-names>Anna M.</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ball</surname>
<given-names>Helen J.</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hunt</surname>
<given-names>Nicholas H.</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ryffel</surname>
<given-names>Bernhard</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Quesniaux</surname>
<given-names>Valerie F. J.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>University of Orléans and CNRS, Molecular Immunology and Embryology UMR6218, Orleans, France</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>CNRS CBM (Centre de Biophysique Moléculaire), Orleans, France</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa</addr-line>
</aff>
<aff id="aff4"><label>4</label>
<addr-line>University of Duesseldorf, Duesseldorf, Germany</addr-line>
</aff>
<aff id="aff5"><label>5</label>
<addr-line>Pasteur Institute Paris, Paris, France</addr-line>
</aff>
<aff id="aff6"><label>6</label>
<addr-line>The University of Sydney, Department of Pathology, Camperdown, Australia</addr-line>
</aff>
<aff id="aff7"><label>7</label>
<addr-line>Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France</addr-line>
</aff>
<aff id="aff8"><label>8</label>
<addr-line>Inserm, U567, Paris, France</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Doolan</surname>
<given-names>Denise L.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">Queensland Institute of Medical Research, Australia</aff>
<author-notes><corresp id="cor1">* E-mail: <email>bryffel@cnrs-orleans.fr</email>
(BR); <email>quesniaux@cnrs-orleans.fr</email>
(VQ)</corresp>
<fn fn-type="con"><p>Conceived and designed the experiments: RM LR JB BR VQ GG DT NH MF VB PL SS AH. Performed the experiments: BD DT MF VB PL LF AH HB. Analyzed the data: RM KP LR JB BR VQ BD GG DT NH MF VB PL LF SS AH HB. Contributed reagents/materials/analysis tools: RM KP LR JB BD NH LF SS HB. Wrote the paper: KP BR VQ GG.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2008</year>
</pub-date>
<pub-date pub-type="epub"><day>9</day>
<month>7</month>
<year>2008</year>
</pub-date>
<volume>3</volume>
<issue>7</issue>
<elocation-id>e2608</elocation-id>
<history><date date-type="received"><day>28</day>
<month>3</month>
<year>2008</year>
</date>
<date date-type="accepted"><day>4</day>
<month>6</month>
<year>2008</year>
</date>
</history>
<copyright-statement>Togbe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</copyright-statement>
<copyright-year>2008</copyright-year>
<abstract><sec><title>Background</title>
<p>TNF-related lymphotoxin α (LTα) is essential for the development of <italic>Plasmodium berghei</italic>
ANKA (PbA)-induced experimental cerebral malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a second arm of LTα-signaling essential for ECM development through LTβ-R, receptor of LTα1β2 heterotrimer.</p>
</sec>
<sec><title>Methodology/Principal Findings</title>
<p>LTβR deficient mice did not develop the neurological signs seen in PbA induced ECM but died at three weeks with high parasitaemia and severe anemia like LTαβ deficient mice. Resistance of LTαβ or LTβR deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin<sup>+</sup>
CD8<sup>+</sup>
T cells, and their ICAM-1 expression were clearly attenuated in the brain of resistant mice. An essential contribution of LIGHT, another LTβR ligand, could be excluded, as LIGHT deficient mice rapidly succumbed to ECM.</p>
</sec>
<sec><title>Conclusions/Significance</title>
<p>LTβR expressed on radioresistant resident stromal, probably endothelial cells, rather than hematopoietic cells, are essential for the development of ECM, as assessed by hematopoietic reconstitution experiment. Therefore, the data suggest that both functional LTβR and TNFR2 signaling are required and non-redundant for the development of microvascular pathology resulting in fatal ECM.</p>
</sec>
</abstract>
<counts><page-count count="12"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001377 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 001377 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Asie |area= AustralieFrV1 |flux= Pmc |étape= Curation |type= RBID |clé= PMC:2442868 |texte= Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:18612394" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \ | NlmPubMed2Wicri -a AustralieFrV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |