Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes
Identifieur interne : 001799 ( Pmc/Corpus ); précédent : 001798; suivant : 001800Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes
Auteurs : Subash Babu ; V. Kumaraswami ; Thomas B. NutmanSource :
- Infection and Immunity [ 0019-9567 ] ; 2005.
Abstract
T-bet (T-box expressed in T cells) and GATA-3 are transcription factors that play a critical role in the development of Th1 and Th2 cells, as do genes of the SOCS (suppressor of cytokine signaling) family, albeit indirectly. Another transcription factor, Foxp3, is a master regulator of natural regulatory T cells (Tregs). To identify the role of these factors in impaired Th1 responses of patent filarial infection, analysis of cytokine, SOCS, and transcription factor mRNA expression was performed on purified T cells of filaria-infected individuals (
Url:
DOI: 10.1128/IAI.73.6.3394-3401.2005
PubMed: 15908366
PubMed Central: 1111868
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PMC:1111868Le document en format XML
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<author><name sortKey="Kumaraswami, V" sort="Kumaraswami, V" uniqKey="Kumaraswami V" first="V." last="Kumaraswami">V. Kumaraswami</name>
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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>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes </title>
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<series><title level="j">Infection and Immunity</title>
<idno type="ISSN">0019-9567</idno>
<idno type="eISSN">1098-5522</idno>
<imprint><date when="2005">2005</date>
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<front><div type="abstract" xml:lang="en"><p>T-bet (T-box expressed in T cells) and GATA-3 are transcription factors that play a critical role in the development of Th1 and Th2 cells, as do genes of the SOCS (suppressor of cytokine signaling) family, albeit indirectly. Another transcription factor, Foxp3, is a master regulator of natural regulatory T cells (Tregs). To identify the role of these factors in impaired Th1 responses of patent filarial infection, analysis of cytokine, SOCS, and transcription factor mRNA expression was performed on purified T cells of filaria-infected individuals (<italic>n</italic>
= 6) and uninfected controls (<italic>n</italic>
= 6). As expected (and in contrast to cells of uninfected individuals), there was a significant depression of gamma interferon (IFN-γ) and a concomitant increase in interleukin-4 (IL-4), IL-5, and IL-10 mRNA expression following stimulation with parasite antigen (BmA) but not with a polyclonal T-cell (anti-CD3) stimulus. T-bet (but not GATA-3) was expressed at significantly lower levels in cells of filaria-infected individuals in response to BmA compared with those from the uninfected group, accounting, at least partially, for the diminished IFN-γ expression. Second, we found no significant differences in expression of Foxp3 between the two groups, although induction of Foxp3 expression correlated with induced expression levels of IL-10, implicating Tregs in the IL-10 expression seen. Finally, parasite-specific T-cell expression of SOCS-1, SOCS-5, and SOCS-7 was significantly diminished among infected patients; in contrast, expression of SOCS-3 increased. Our data therefore indicate that the impaired Th1 responses observed in patent lymphatic filariasis are associated with decreased expression of T-bet, SOCS-1, SOCS-5, and SOCS-7 and increased expression of SOCS-3 in T cells.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Infect Immun</journal-id>
<journal-id journal-id-type="publisher-id">iai</journal-id>
<journal-title>Infection and Immunity</journal-title>
<issn pub-type="ppub">0019-9567</issn>
<issn pub-type="epub">1098-5522</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">15908366</article-id>
<article-id pub-id-type="pmc">1111868</article-id>
<article-id pub-id-type="publisher-id">1977-04</article-id>
<article-id pub-id-type="doi">10.1128/IAI.73.6.3394-3401.2005</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Fungal and Parasitic Infections</subject>
</subj-group>
</article-categories>
<title-group><article-title>Transcriptional Control of Impaired Th1 Responses in Patent Lymphatic Filariasis by T-Box Expressed in T Cells and Suppressor of Cytokine Signaling Genes </article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Babu</surname>
<given-names>Subash</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kumaraswami</surname>
<given-names>V.</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nutman</surname>
<given-names>Thomas B.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
</contrib-group>
<aff id="aff1">Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,<label>1</label>
Tuberculosis Research Center, Chennai, India<label>2</label>
</aff>
<author-notes><fn id="cor1"><label>*</label>
<p>Corresponding author. Mailing address: LPD, NIAID, 4 Center Drive, Room 4/B1-05, NIH, Bethesda, MD 20892-0425. Phone: (301) 435-8649. Fax: (301) 480-3757. E-mail: <email>sbabu@niaid.nih.gov</email>
.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>6</month>
<year>2005</year>
</pub-date>
<volume>73</volume>
<issue>6</issue>
<fpage>3394</fpage>
<lpage>3401</lpage>
<history><date date-type="received"><day>17</day>
<month>11</month>
<year>2004</year>
</date>
<date date-type="rev-recd"><day>4</day>
<month>1</month>
<year>2005</year>
</date>
<date date-type="accepted"><day>20</day>
<month>1</month>
<year>2005</year>
</date>
</history>
<copyright-statement>Copyright © 2005, American Society for Microbiology</copyright-statement>
<copyright-year>2005</copyright-year>
<abstract><p>T-bet (T-box expressed in T cells) and GATA-3 are transcription factors that play a critical role in the development of Th1 and Th2 cells, as do genes of the SOCS (suppressor of cytokine signaling) family, albeit indirectly. Another transcription factor, Foxp3, is a master regulator of natural regulatory T cells (Tregs). To identify the role of these factors in impaired Th1 responses of patent filarial infection, analysis of cytokine, SOCS, and transcription factor mRNA expression was performed on purified T cells of filaria-infected individuals (<italic>n</italic>
= 6) and uninfected controls (<italic>n</italic>
= 6). As expected (and in contrast to cells of uninfected individuals), there was a significant depression of gamma interferon (IFN-γ) and a concomitant increase in interleukin-4 (IL-4), IL-5, and IL-10 mRNA expression following stimulation with parasite antigen (BmA) but not with a polyclonal T-cell (anti-CD3) stimulus. T-bet (but not GATA-3) was expressed at significantly lower levels in cells of filaria-infected individuals in response to BmA compared with those from the uninfected group, accounting, at least partially, for the diminished IFN-γ expression. Second, we found no significant differences in expression of Foxp3 between the two groups, although induction of Foxp3 expression correlated with induced expression levels of IL-10, implicating Tregs in the IL-10 expression seen. Finally, parasite-specific T-cell expression of SOCS-1, SOCS-5, and SOCS-7 was significantly diminished among infected patients; in contrast, expression of SOCS-3 increased. Our data therefore indicate that the impaired Th1 responses observed in patent lymphatic filariasis are associated with decreased expression of T-bet, SOCS-1, SOCS-5, and SOCS-7 and increased expression of SOCS-3 in T cells.</p>
</abstract>
</article-meta>
<notes><fn-group><fn><p><italic>Editor:</italic>
J. F. Urban, Jr.</p>
</fn>
</fn-group>
</notes>
</front>
</pmc>
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