Lymphangiogenesis and Lymphatic Remodeling Induced by Filarial Parasites: Implications for Pathogenesis
Identifieur interne : 006205 ( Main/Exploration ); précédent : 006204; suivant : 006206Lymphangiogenesis and Lymphatic Remodeling Induced by Filarial Parasites: Implications for Pathogenesis
Auteurs : Sasisekhar Bennuru ; Thomas B. NutmanSource :
- PLoS Pathogens [ 1553-7366 ] ; 2009.
Descripteurs français
- KwdFr :
- Cellules endothéliales (anatomopathologie), Cellules endothéliales (immunologie), Cellules endothéliales (parasitologie), Cytométrie en flux, Différenciation cellulaire (immunologie), Expression des gènes (immunologie), Filariose lymphatique (anatomopathologie), Filariose lymphatique (génétique), Filariose lymphatique (immunologie), Humains, Inhibiteur tissulaire de métalloprotéinase-1 (biosynthèse), Inhibiteur tissulaire de métalloprotéinase-1 (immunologie), Inhibiteur tissulaire de métalloprotéinase-2 (biosynthèse), Inhibiteur tissulaire de métalloprotéinase-2 (immunologie), Lymphangiogenèse (immunologie), Matrix metalloproteinase 1 (biosynthèse), Matrix metalloproteinase 1 (immunologie), Matrix metalloproteinase 2 (biosynthèse), Matrix metalloproteinase 2 (immunologie), Microscopie confocale, Prolifération cellulaire, RT-PCR, Séparation cellulaire, Séquençage par oligonucléotides en batterie.
- MESH :
- anatomopathologie : Cellules endothéliales, Filariose lymphatique.
- biosynthèse : Inhibiteur tissulaire de métalloprotéinase-1, Inhibiteur tissulaire de métalloprotéinase-2, Matrix metalloproteinase 1, Matrix metalloproteinase 2.
- génétique : Filariose lymphatique.
- immunologie : Cellules endothéliales, Différenciation cellulaire, Expression des gènes, Filariose lymphatique, Inhibiteur tissulaire de métalloprotéinase-1, Inhibiteur tissulaire de métalloprotéinase-2, Lymphangiogenèse, Matrix metalloproteinase 1, Matrix metalloproteinase 2.
- parasitologie : Cellules endothéliales.
- Cytométrie en flux, Humains, Microscopie confocale, Prolifération cellulaire, RT-PCR, Séparation cellulaire, Séquençage par oligonucléotides en batterie.
English descriptors
- KwdEn :
- Cell Differentiation (immunology), Cell Proliferation, Cell Separation, Elephantiasis, Filarial (genetics), Elephantiasis, Filarial (immunology), Elephantiasis, Filarial (pathology), Endothelial Cells (immunology), Endothelial Cells (parasitology), Endothelial Cells (pathology), Flow Cytometry, Gene Expression (immunology), Humans, Lymphangiogenesis (immunology), Matrix Metalloproteinase 1 (biosynthesis), Matrix Metalloproteinase 1 (immunology), Matrix Metalloproteinase 2 (biosynthesis), Matrix Metalloproteinase 2 (immunology), Microscopy, Confocal, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Tissue Inhibitor of Metalloproteinase-1 (biosynthesis), Tissue Inhibitor of Metalloproteinase-1 (immunology), Tissue Inhibitor of Metalloproteinase-2 (biosynthesis), Tissue Inhibitor of Metalloproteinase-2 (immunology).
- MESH :
- chemical , biosynthesis : Matrix Metalloproteinase 1, Matrix Metalloproteinase 2, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2.
- genetics : Elephantiasis, Filarial.
- immunology : Cell Differentiation, Elephantiasis, Filarial, Endothelial Cells, Gene Expression, Lymphangiogenesis, Matrix Metalloproteinase 1, Matrix Metalloproteinase 2, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2.
- parasitology : Endothelial Cells.
- pathology : Elephantiasis, Filarial, Endothelial Cells.
- Cell Proliferation, Cell Separation, Flow Cytometry, Humans, Microscopy, Confocal, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction.
Abstract
Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures
Url:
DOI: 10.1371/journal.ppat.1000688
PubMed: 20011114
PubMed Central: 2781552
Affiliations:
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Le document en format XML
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Nutman</name><affiliation><nlm:aff id="aff1"></nlm:aff></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="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Differentiation (immunology)</term><term>Cell Proliferation</term><term>Cell Separation</term><term>Elephantiasis, Filarial (genetics)</term><term>Elephantiasis, Filarial (immunology)</term><term>Elephantiasis, Filarial (pathology)</term><term>Endothelial Cells (immunology)</term><term>Endothelial Cells (parasitology)</term><term>Endothelial Cells (pathology)</term><term>Flow Cytometry</term><term>Gene Expression (immunology)</term><term>Humans</term><term>Lymphangiogenesis (immunology)</term><term>Matrix Metalloproteinase 1 (biosynthesis)</term><term>Matrix Metalloproteinase 1 (immunology)</term><term>Matrix Metalloproteinase 2 (biosynthesis)</term><term>Matrix Metalloproteinase 2 (immunology)</term><term>Microscopy, Confocal</term><term>Oligonucleotide Array Sequence Analysis</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Tissue Inhibitor of Metalloproteinase-1 (biosynthesis)</term><term>Tissue Inhibitor of Metalloproteinase-1 (immunology)</term><term>Tissue Inhibitor of Metalloproteinase-2 (biosynthesis)</term><term>Tissue Inhibitor of Metalloproteinase-2 (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cellules endothéliales (anatomopathologie)</term><term>Cellules endothéliales (immunologie)</term><term>Cellules endothéliales (parasitologie)</term><term>Cytométrie en flux</term><term>Différenciation cellulaire (immunologie)</term><term>Expression des gènes (immunologie)</term><term>Filariose lymphatique (anatomopathologie)</term><term>Filariose lymphatique (génétique)</term><term>Filariose lymphatique (immunologie)</term><term>Humains</term><term>Inhibiteur tissulaire de métalloprotéinase-1 (biosynthèse)</term><term>Inhibiteur tissulaire de métalloprotéinase-1 (immunologie)</term><term>Inhibiteur tissulaire de métalloprotéinase-2 (biosynthèse)</term><term>Inhibiteur tissulaire de métalloprotéinase-2 (immunologie)</term><term>Lymphangiogenèse (immunologie)</term><term>Matrix metalloproteinase 1 (biosynthèse)</term><term>Matrix metalloproteinase 1 (immunologie)</term><term>Matrix metalloproteinase 2 (biosynthèse)</term><term>Matrix metalloproteinase 2 (immunologie)</term><term>Microscopie confocale</term><term>Prolifération cellulaire</term><term>RT-PCR</term><term>Séparation cellulaire</term><term>Séquençage par oligonucléotides en batterie</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Matrix Metalloproteinase 1</term><term>Matrix Metalloproteinase 2</term><term>Tissue Inhibitor of Metalloproteinase-1</term><term>Tissue Inhibitor of Metalloproteinase-2</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Cellules endothéliales</term><term>Filariose lymphatique</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Inhibiteur tissulaire de métalloprotéinase-1</term><term>Inhibiteur tissulaire de métalloprotéinase-2</term><term>Matrix metalloproteinase 1</term><term>Matrix metalloproteinase 2</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Elephantiasis, Filarial</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Filariose lymphatique</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules endothéliales</term><term>Différenciation cellulaire</term><term>Expression des gènes</term><term>Filariose lymphatique</term><term>Inhibiteur tissulaire de métalloprotéinase-1</term><term>Inhibiteur tissulaire de métalloprotéinase-2</term><term>Lymphangiogenèse</term><term>Matrix metalloproteinase 1</term><term>Matrix metalloproteinase 2</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cell Differentiation</term><term>Elephantiasis, Filarial</term><term>Endothelial Cells</term><term>Gene Expression</term><term>Lymphangiogenesis</term><term>Matrix Metalloproteinase 1</term><term>Matrix Metalloproteinase 2</term><term>Tissue Inhibitor of Metalloproteinase-1</term><term>Tissue Inhibitor of Metalloproteinase-2</term></keywords><keywords scheme="MESH" qualifier="parasitologie" xml:lang="fr"><term>Cellules endothéliales</term></keywords><keywords scheme="MESH" qualifier="parasitology" xml:lang="en"><term>Endothelial Cells</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Elephantiasis, Filarial</term><term>Endothelial Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Proliferation</term><term>Cell Separation</term><term>Flow Cytometry</term><term>Humans</term><term>Microscopy, Confocal</term><term>Oligonucleotide Array Sequence Analysis</term><term>Reverse Transcriptase Polymerase Chain Reaction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cytométrie en flux</term><term>Humains</term><term>Microscopie confocale</term><term>Prolifération cellulaire</term><term>RT-PCR</term><term>Séparation cellulaire</term><term>Séquençage par oligonucléotides en batterie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Even in the absence of an adaptive immune system in murine models, lymphatic dilatation and dysfunction occur in filarial infections, although severe irreversible lymphedema and elephantiasis appears to require an intact adaptive immune response in human infections. To address how filarial parasites and their antigens influence the lymphatics directly, human lymphatic endothelial cells were exposed to filarial antigens, live parasites, or infected patient serum. Live filarial parasites or filarial antigens induced both significant LEC proliferation and differentiation into tube-like structures <italic>in vitro</italic>. Moreover, serum from patently infected (microfilaria positive) patients and those with longstanding chronic lymphatic obstruction induced significantly increased LEC proliferation compared to sera from uninfected individuals. Differentiation of LEC into tube-like networks was found to be associated with significantly increased levels of matrix metalloproteases and inhibition of their TIMP inhibitors (Tissue inhibitors of matrix metalloproteases). Comparison of global gene expression induced by live parasites in LEC to parasite-unexposed LEC demonstrated that filarial parasites altered the expression of those genes involved in cellular organization and development as well as those associated with junction adherence pathways that in turn decreased trans-endothelial transport as assessed by FITC-Dextran. The data suggest that filarial parasites directly induce lymphangiogenesis and lymphatic differentiation and provide insight into the mechanisms underlying the pathology seen in lymphatic filariasis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Rajan, Tv" uniqKey="Rajan T">TV Rajan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Connor, Dh" uniqKey="Connor D">DH Connor</name></author><author><name sortKey="Palmieri, Jr" uniqKey="Palmieri J">JR Palmieri</name></author><author><name sortKey="Gibson, Dw" uniqKey="Gibson D">DW Gibson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lichtenberg, F" uniqKey="Lichtenberg F">F Lichtenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klei, Tr" uniqKey="Klei T">TR Klei</name></author><author><name sortKey="Enright, Fm" uniqKey="Enright F">FM Enright</name></author><author><name sortKey="Blanchard, Dp" uniqKey="Blanchard D">DP Blanchard</name></author><author><name sortKey="Uhl, Sa" uniqKey="Uhl S">SA Uhl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nutman, Tb" uniqKey="Nutman T">TB Nutman</name></author><author><name sortKey="Kumaraswami, V" uniqKey="Kumaraswami V">V Kumaraswami</name></author><author><name sortKey="Pao, L" uniqKey="Pao L">L Pao</name></author><author><name sortKey="Narayanan, Pr" uniqKey="Narayanan P">PR Narayanan</name></author><author><name sortKey="Ottesen, Ea" uniqKey="Ottesen E">EA Ottesen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ottesen, Ea" uniqKey="Ottesen E">EA Ottesen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Piessens, Wf" uniqKey="Piessens W">WF Piessens</name></author><author><name sortKey="Mcgreevy, Pb" uniqKey="Mcgreevy P">PB McGreevy</name></author><author><name sortKey="Piessens, Pw" uniqKey="Piessens P">PW Piessens</name></author><author><name sortKey="Mcgreevy, M" uniqKey="Mcgreevy M">M McGreevy</name></author><author><name sortKey="Koiman, I" uniqKey="Koiman I">I Koiman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nelson, Fk" uniqKey="Nelson F">FK Nelson</name></author><author><name sortKey="Greiner, Dl" uniqKey="Greiner D">DL Greiner</name></author><author><name sortKey="Shultz, Ld" uniqKey="Shultz L">LD Shultz</name></author><author><name sortKey="Rajan, Tv" uniqKey="Rajan T">TV Rajan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vincent, Al" uniqKey="Vincent A">AL Vincent</name></author><author><name sortKey="Vickery, Ac" uniqKey="Vickery A">AC Vickery</name></author><author><name sortKey="Lotz, Mj" uniqKey="Lotz M">MJ Lotz</name></author><author><name sortKey="Desai, U" uniqKey="Desai U">U Desai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vickery, Ac" uniqKey="Vickery A">AC Vickery</name></author><author><name sortKey="Albertine, Kh" uniqKey="Albertine K">KH Albertine</name></author><author><name sortKey="Nayar, Jk" uniqKey="Nayar J">JK Nayar</name></author><author><name sortKey="Kwa, Bh" uniqKey="Kwa B">BH Kwa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vickery, Ac" uniqKey="Vickery A">AC Vickery</name></author><author><name sortKey="Vincent, Al" uniqKey="Vincent A">AL Vincent</name></author><author><name sortKey="Sodeman, Wa" uniqKey="Sodeman W">WA Sodeman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Freedman, Do" uniqKey="Freedman D">DO Freedman</name></author><author><name sortKey="De Almeido Filho, Pj" uniqKey="De Almeido Filho P">PJ de Almeido Filho</name></author><author><name sortKey="Besh, S" uniqKey="Besh S">S Besh</name></author><author><name sortKey="Maia E Silva, Mc" uniqKey="Maia E Silva M">MC Maia e Silva</name></author><author><name 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uniqKey="Hussain R">R Hussain</name></author><author><name sortKey="Hamilton, Rg" uniqKey="Hamilton R">RG Hamilton</name></author><author><name sortKey="Kumaraswami, V" uniqKey="Kumaraswami V">V Kumaraswami</name></author><author><name sortKey="Adkinson, Nf" uniqKey="Adkinson N">NF Adkinson</name></author><author><name sortKey="Ottesen, Ea" uniqKey="Ottesen E">EA Ottesen</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Bennuru, Sasisekhar" sort="Bennuru, Sasisekhar" uniqKey="Bennuru S" first="Sasisekhar" last="Bennuru">Sasisekhar Bennuru</name><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. 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