Parasite-Antigen Driven Expansion of IL-5− and IL-5+ Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGFβ
Identifieur interne : 002732 ( Main/Exploration ); précédent : 002731; suivant : 002733Parasite-Antigen Driven Expansion of IL-5− and IL-5+ Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGFβ
Auteurs : Rajamanickam Anuradha [Inde] ; Parakkal Jovvian George [Inde] ; Luke E. Hanna [États-Unis] ; Vedachalam Chandrasekaran [Inde] ; P. Paul Kumaran [Inde] ; Thomas B. Nutman [États-Unis] ; Subash Babu [Inde, États-Unis]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Animaux, Antigènes d'helminthe (immunologie), Facteur de croissance transformant bêta (métabolisme), Femelle, Filariose lymphatique (immunologie), Humains, Interleukine-10 (métabolisme), Interleukine-5 (analyse), Jeune adulte, Lymphocytes auxiliaires Th2 (), Lymphocytes auxiliaires Th2 (immunologie), Mâle, Sous-populations de lymphocytes T (), Sous-populations de lymphocytes T (immunologie), Sujet âgé.
- MESH :
- analyse : Interleukine-5.
- immunologie : Antigènes d'helminthe, Filariose lymphatique, Lymphocytes auxiliaires Th2, Sous-populations de lymphocytes T.
- métabolisme : Facteur de croissance transformant bêta, Interleukine-10.
- Adulte, Adulte d'âge moyen, Animaux, Femelle, Humains, Jeune adulte, Lymphocytes auxiliaires Th2, Mâle, Sous-populations de lymphocytes T, Sujet âgé.
English descriptors
- KwdEn :
- Adult, Aged, Animals, Antigens, Helminth (immunology), Elephantiasis, Filarial (immunology), Female, Humans, Interleukin-10 (metabolism), Interleukin-5 (analysis), Male, Middle Aged, T-Lymphocyte Subsets (chemistry), T-Lymphocyte Subsets (immunology), Th2 Cells (chemistry), Th2 Cells (immunology), Transforming Growth Factor beta (metabolism), Young Adult.
- MESH :
- chemical , analysis : Interleukin-5.
- chemical , immunology : Antigens, Helminth.
- chemistry : T-Lymphocyte Subsets, Th2 Cells.
- immunology : Elephantiasis, Filarial, T-Lymphocyte Subsets, Th2 Cells.
- chemical , metabolism : Interleukin-10, Transforming Growth Factor beta.
- Adult, Aged, Animals, Female, Humans, Male, Middle Aged, Young Adult.
Abstract
Two different Th2 subsets have been defined recently on the basis of IL-5 expression – an IL-5+Th2 subset and an IL-5−Th2 subset in the setting of allergy. However, the role of these newly described CD4+ T cells subpopulations has not been explored in other contexts.
To study the role of the Th2 subpopulation in a chronic, tissue invasive parasitic infection (lymphatic filariasis), we examined the frequency of IL-5+IL-4+IL-13+ CD4+ T cells and IL-5−IL-4 IL-13+ CD4+ T cells in asymptomatic, infected individuals (INF) and compared them to frequencies (Fo) in filarial-uninfected (UN) individuals and to those with filarial lymphedema (CP).
INF individuals exhibited a significant increase in the spontaneously expressed and antigen-induced Fo of both Th2 subpopulations compared to the UN and CP. Interestingly, there was a positive correlation between the Fo of IL-5+Th2 cells and the absolute eosinophil and neutrophil counts; in addition there was a positive correlation between the frequency of the CD4+IL-5−Th2 subpopulation and the levels of parasite antigen – specific IgE and IgG4 in INF individuals. Moreover, blockade of IL-10 and/or TGFβ demonstrated that each of these 2 regulatory cytokines exert opposite effects on the different Th2 subsets. Finally, in those INF individuals cured of infection by anti-filarial therapy, there was a significantly decreased Fo of both Th2 subsets.
Our findings suggest that both IL-5+ and IL-5−Th2 cells play an important role in the regulation of immune responses in filarial infection and that these two Th2 subpopulations may be regulated by different cytokine-receptor mediated processes.
Url:
DOI: 10.1371/journal.pntd.0002658
PubMed: 24498448
PubMed Central: 3907332
Affiliations:
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Hanna</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Laboratory of Parasitic Diseases, National Institutes 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 Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Chandrasekaran, Vedachalam" sort="Chandrasekaran, Vedachalam" uniqKey="Chandrasekaran V" first="Vedachalam" last="Chandrasekaran">Vedachalam Chandrasekaran</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>National Institute for Research in Tuberculosis, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institute for Research in Tuberculosis, Chennai</wicri:regionArea><wicri:noRegion>Chennai</wicri:noRegion></affiliation></author><author><name sortKey="Kumaran, P Paul" sort="Kumaran, P Paul" uniqKey="Kumaran P" first="P. Paul" last="Kumaran">P. Paul Kumaran</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>National Institute for Research in Tuberculosis, Chennai, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>National Institute for Research in Tuberculosis, 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="aff2"><addr-line>Laboratory of Parasitic Diseases, National Institutes 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 Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</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="2"><nlm:aff id="aff2"><addr-line>Laboratory of Parasitic Diseases, National Institutes 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 Institutes 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="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Antigens, Helminth (immunology)</term><term>Elephantiasis, Filarial (immunology)</term><term>Female</term><term>Humans</term><term>Interleukin-10 (metabolism)</term><term>Interleukin-5 (analysis)</term><term>Male</term><term>Middle Aged</term><term>T-Lymphocyte Subsets (chemistry)</term><term>T-Lymphocyte Subsets (immunology)</term><term>Th2 Cells (chemistry)</term><term>Th2 Cells (immunology)</term><term>Transforming Growth Factor beta (metabolism)</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Animaux</term><term>Antigènes d'helminthe (immunologie)</term><term>Facteur de croissance transformant bêta (métabolisme)</term><term>Femelle</term><term>Filariose lymphatique (immunologie)</term><term>Humains</term><term>Interleukine-10 (métabolisme)</term><term>Interleukine-5 (analyse)</term><term>Jeune adulte</term><term>Lymphocytes auxiliaires Th2 ()</term><term>Lymphocytes auxiliaires Th2 (immunologie)</term><term>Mâle</term><term>Sous-populations de lymphocytes T ()</term><term>Sous-populations de lymphocytes T (immunologie)</term><term>Sujet âgé</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Interleukin-5</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Helminth</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Interleukine-5</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>T-Lymphocyte Subsets</term><term>Th2 Cells</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes d'helminthe</term><term>Filariose lymphatique</term><term>Lymphocytes auxiliaires Th2</term><term>Sous-populations de lymphocytes T</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Elephantiasis, Filarial</term><term>T-Lymphocyte Subsets</term><term>Th2 Cells</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Interleukin-10</term><term>Transforming Growth Factor beta</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de croissance transformant bêta</term><term>Interleukine-10</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Animals</term><term>Female</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>Animaux</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Lymphocytes auxiliaires Th2</term><term>Mâle</term><term>Sous-populations de lymphocytes T</term><term>Sujet âgé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Two different Th2 subsets have been defined recently on the basis of IL-5 expression – an IL-5<sup>+</sup>Th2 subset and an IL-5<sup>−</sup>Th2 subset in the setting of allergy. However, the role of these newly described CD4<sup>+</sup> T cells subpopulations has not been explored in other contexts.</p></sec><sec><title>Methods</title><p>To study the role of the Th2 subpopulation in a chronic, tissue invasive parasitic infection (lymphatic filariasis), we examined the frequency of IL-5<sup>+</sup>IL-4<sup>+</sup>IL-13<sup>+</sup> CD4<sup>+</sup> T cells and IL-5<sup>−</sup>IL-4 IL-13<sup>+</sup> CD4<sup>+</sup> T cells in asymptomatic, infected individuals (INF) and compared them to frequencies (F<sub>o</sub>) in filarial-uninfected (UN) individuals and to those with filarial lymphedema (CP).</p></sec><sec><title>Results</title><p>INF individuals exhibited a significant increase in the spontaneously expressed and antigen-induced F<sub>o</sub> of both Th2 subpopulations compared to the UN and CP. Interestingly, there was a positive correlation between the F<sub>o</sub> of IL-5<sup>+</sup>Th2 cells and the absolute eosinophil and neutrophil counts; in addition there was a positive correlation between the frequency of the CD4<sup>+</sup>IL-5<sup>−</sup>Th2 subpopulation and the levels of parasite antigen – specific IgE and IgG4 in INF individuals. Moreover, blockade of IL-10 and/or TGFβ demonstrated that each of these 2 regulatory cytokines exert opposite effects on the different Th2 subsets. Finally, in those INF individuals cured of infection by anti-filarial therapy, there was a significantly decreased F<sub>o</sub> of both Th2 subsets.</p></sec><sec><title>Conclusions</title><p>Our findings suggest that both IL-5<sup>+</sup> and IL-5<sup>−</sup>Th2 cells play an important role in the regulation of immune responses in filarial infection and that these two Th2 subpopulations may be regulated by different cytokine-receptor mediated processes.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mosmann, Tr" uniqKey="Mosmann T">TR Mosmann</name></author><author><name sortKey="Cherwinski, H" uniqKey="Cherwinski H">H Cherwinski</name></author><author><name sortKey="Bond, Mw" uniqKey="Bond M">MW Bond</name></author><author><name sortKey="Giedlin, Ma" uniqKey="Giedlin M">MA Giedlin</name></author><author><name sortKey="Coffman, Rl" uniqKey="Coffman R">RL 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sortKey="Naumann, R" uniqKey="Naumann R">R Naumann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Qaoud, Km" uniqKey="Al Qaoud K">KM Al-Qaoud</name></author><author><name sortKey="Pearlman, E" uniqKey="Pearlman E">E Pearlman</name></author><author><name sortKey="Hartung, T" uniqKey="Hartung T">T Hartung</name></author><author><name sortKey="Klukowski, J" uniqKey="Klukowski J">J Klukowski</name></author><author><name sortKey="Fleischer, B" uniqKey="Fleischer B">B Fleischer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Padigel, Um" uniqKey="Padigel U">UM Padigel</name></author><author><name sortKey="Stein, L" uniqKey="Stein L">L Stein</name></author><author><name sortKey="Redding, K" uniqKey="Redding K">K Redding</name></author><author><name sortKey="Lee, Jj" uniqKey="Lee J">JJ Lee</name></author><author><name sortKey="Nolan, Tj" uniqKey="Nolan T">TJ Nolan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maizels, Rm" uniqKey="Maizels R">RM Maizels</name></author><author><name sortKey="Yazdanbakhsh, M" uniqKey="Yazdanbakhsh M">M Yazdanbakhsh</name></author></analytic></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="Anuradha, Rajamanickam" sort="Anuradha, Rajamanickam" uniqKey="Anuradha R" first="Rajamanickam" last="Anuradha">Rajamanickam Anuradha</name></noRegion><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name><name sortKey="Chandrasekaran, Vedachalam" sort="Chandrasekaran, Vedachalam" uniqKey="Chandrasekaran V" first="Vedachalam" last="Chandrasekaran">Vedachalam Chandrasekaran</name><name sortKey="George, Parakkal Jovvian" sort="George, Parakkal Jovvian" uniqKey="George P" first="Parakkal Jovvian" last="George">Parakkal Jovvian George</name><name sortKey="Kumaran, P Paul" sort="Kumaran, P Paul" uniqKey="Kumaran P" first="P. Paul" last="Kumaran">P. Paul Kumaran</name></country><country name="États-Unis"><region name="Maryland"><name sortKey="Hanna, Luke E" sort="Hanna, Luke E" uniqKey="Hanna L" first="Luke E." last="Hanna">Luke E. Hanna</name></region><name sortKey="Babu, Subash" sort="Babu, Subash" uniqKey="Babu S" first="Subash" last="Babu">Subash Babu</name><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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