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 : 002736 ( Main/Merge ); précédent : 002735; suivant : 002737Parasite-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
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PMC:3907332Le document en format XML
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Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGFβ</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Parasite-Antigen Driven Expansion of IL-5<sup>−</sup>
and IL-5<sup>+</sup>
Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGFβ</title>
<author><name sortKey="Anuradha, Rajamanickam" sort="Anuradha, Rajamanickam" uniqKey="Anuradha R" first="Rajamanickam" last="Anuradha">Rajamanickam Anuradha</name>
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<author><name sortKey="George, Parakkal Jovvian" sort="George, Parakkal Jovvian" uniqKey="George P" first="Parakkal Jovvian" last="George">Parakkal Jovvian George</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>
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<country xml:lang="fr">Inde</country>
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<author><name sortKey="Hanna, Luke E" sort="Hanna, Luke E" uniqKey="Hanna L" first="Luke E." last="Hanna">Luke E. Hanna</name>
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</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>
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</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>
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<country xml:lang="fr">Inde</country>
<wicri:regionArea>National Institute for Research in Tuberculosis, Chennai</wicri:regionArea>
<wicri:noRegion>Chennai</wicri:noRegion>
</affiliation>
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<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>
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<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>
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<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>
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<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>
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<author><name sortKey="Kruize, Yc" uniqKey="Kruize Y">YC Kruize</name>
</author>
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