Filarial Lymphedema Is Characterized by Antigen-Specific Th1 and Th17 Proinflammatory Responses and a Lack of Regulatory T Cells
Identifieur interne : 006279 ( Main/Exploration ); précédent : 006278; suivant : 006280Filarial Lymphedema Is Characterized by Antigen-Specific Th1 and Th17 Proinflammatory Responses and a Lack of Regulatory T Cells
Auteurs : Subash Babu [Inde, États-Unis] ; Sajid Q. Bhat [Inde] ; N. Pavan Kumar [Inde] ; Angelo B. Lipira [Inde] ; Sanath Kumar [Inde] ; C. Karthik [Inde] ; V. Kumaraswami [Inde] ; Thomas B. Nutman [États-Unis]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2009.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Analyse de profil d'expression de gènes, Antigènes d'helminthe (immunologie), Cytokines (biosynthèse), Femelle, Filarioses (anatomopathologie), Filarioses (immunologie), Humains, Inflammation (anatomopathologie), Inflammation (immunologie), Jeune adulte, Lymphoedème (anatomopathologie), Lymphoedème (immunologie), Mâle, Récepteurs immunologiques (biosynthèse), Sous-populations de lymphocytes T (immunologie).
- MESH :
- anatomopathologie : Filarioses, Inflammation, Lymphoedème.
- biosynthèse : Cytokines, Récepteurs immunologiques.
- immunologie : Antigènes d'helminthe, Filarioses, Inflammation, Lymphoedème, Sous-populations de lymphocytes T.
- Adulte, Adulte d'âge moyen, Analyse de profil d'expression de gènes, Femelle, Humains, Jeune adulte, Mâle.
English descriptors
- KwdEn :
- Adult, Antigens, Helminth (immunology), Cytokines (biosynthesis), Female, Filariasis (immunology), Filariasis (pathology), Gene Expression Profiling, Humans, Inflammation (immunology), Inflammation (pathology), Lymphedema (immunology), Lymphedema (pathology), Male, Middle Aged, Receptors, Immunologic (biosynthesis), T-Lymphocyte Subsets (immunology), Young Adult.
- MESH :
- chemical , biosynthesis : Cytokines, Receptors, Immunologic.
- chemical , immunology : Antigens, Helminth.
- immunology : Filariasis, Inflammation, Lymphedema, T-Lymphocyte Subsets.
- pathology : Filariasis, Inflammation, Lymphedema.
- Adult, Female, Gene Expression Profiling, Humans, Male, Middle Aged, Young Adult.
Abstract
Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.
To elucidate the role of CD4+ T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1–10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher production of Th1-type cytokines—IFN-γ and TNF-α—in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines—IL-17A, IL-17F, IL-21, and IL-23—was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFβ, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls.
Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema.
Url:
DOI: 10.1371/journal.pntd.0000420
PubMed: 19381284
PubMed Central: 2666805
Affiliations:
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Bhat</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health–International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health–International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Pavan Kumar, N" sort="Pavan Kumar, N" uniqKey="Pavan Kumar N" first="N." last="Pavan Kumar">N. Pavan Kumar</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health–International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health–International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Lipira, Angelo B" sort="Lipira, Angelo B" uniqKey="Lipira A" first="Angelo B." last="Lipira">Angelo B. Lipira</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health–International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health–International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Kumar, Sanath" sort="Kumar, Sanath" uniqKey="Kumar S" first="Sanath" last="Kumar">Sanath Kumar</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health–International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health–International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Karthik, C" sort="Karthik, C" uniqKey="Karthik C" first="C." last="Karthik">C. Karthik</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health–International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health–International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Kumaraswami, V" sort="Kumaraswami, V" uniqKey="Kumaraswami V" first="V." last="Kumaraswami">V. Kumaraswami</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Institutes of Health–International Center for Excellence in Research, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institutes of Health–International Center for Excellence in Research, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Tuberculosis Research Center, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Tuberculosis Research Center, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name><affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">PLoS Neglected Tropical Diseases</title><idno type="ISSN">1935-2727</idno><idno type="eISSN">1935-2735</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Antigens, Helminth (immunology)</term><term>Cytokines (biosynthesis)</term><term>Female</term><term>Filariasis (immunology)</term><term>Filariasis (pathology)</term><term>Gene Expression Profiling</term><term>Humans</term><term>Inflammation (immunology)</term><term>Inflammation (pathology)</term><term>Lymphedema (immunology)</term><term>Lymphedema (pathology)</term><term>Male</term><term>Middle Aged</term><term>Receptors, Immunologic (biosynthesis)</term><term>T-Lymphocyte Subsets (immunology)</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de profil d'expression de gènes</term><term>Antigènes d'helminthe (immunologie)</term><term>Cytokines (biosynthèse)</term><term>Femelle</term><term>Filarioses (anatomopathologie)</term><term>Filarioses (immunologie)</term><term>Humains</term><term>Inflammation (anatomopathologie)</term><term>Inflammation (immunologie)</term><term>Jeune adulte</term><term>Lymphoedème (anatomopathologie)</term><term>Lymphoedème (immunologie)</term><term>Mâle</term><term>Récepteurs immunologiques (biosynthèse)</term><term>Sous-populations de lymphocytes T (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cytokines</term><term>Receptors, Immunologic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Helminth</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Filarioses</term><term>Inflammation</term><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Cytokines</term><term>Récepteurs immunologiques</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes d'helminthe</term><term>Filarioses</term><term>Inflammation</term><term>Lymphoedème</term><term>Sous-populations de lymphocytes T</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Filariasis</term><term>Inflammation</term><term>Lymphedema</term><term>T-Lymphocyte Subsets</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Filariasis</term><term>Inflammation</term><term>Lymphedema</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Female</term><term>Gene Expression Profiling</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de profil d'expression de gènes</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Mâle</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.</p></sec><sec><title>Methods and Findings</title><p>To elucidate the role of CD4<sup>+</sup> T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1–10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher production of Th1-type cytokines—IFN-γ and TNF-α—in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines—IL-17A, IL-17F, IL-21, and IL-23—was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFβ, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls.</p></sec><sec><title>Conclusion</title><p>Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema.</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></listBibl></div1></back></TEI><affiliations><list><country><li>Inde</li><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="Inde"><noRegion><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name></noRegion><name sortKey="Bhat, Sajid Q" sort="Bhat, Sajid Q" uniqKey="Bhat S" first="Sajid Q." last="Bhat">Sajid Q. Bhat</name><name sortKey="Karthik, C" sort="Karthik, C" uniqKey="Karthik C" first="C." last="Karthik">C. Karthik</name><name sortKey="Kumar, Sanath" sort="Kumar, Sanath" uniqKey="Kumar S" first="Sanath" last="Kumar">Sanath Kumar</name><name sortKey="Kumaraswami, V" sort="Kumaraswami, V" uniqKey="Kumaraswami V" first="V." last="Kumaraswami">V. Kumaraswami</name><name sortKey="Kumaraswami, V" sort="Kumaraswami, V" uniqKey="Kumaraswami V" first="V." last="Kumaraswami">V. Kumaraswami</name><name sortKey="Lipira, Angelo B" sort="Lipira, Angelo B" uniqKey="Lipira A" first="Angelo B." last="Lipira">Angelo B. Lipira</name><name sortKey="Pavan Kumar, N" sort="Pavan Kumar, N" uniqKey="Pavan Kumar N" first="N." last="Pavan Kumar">N. Pavan Kumar</name></country><country name="États-Unis"><region name="Maryland"><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name></region><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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