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Plasmacytoid Dendritic Cells Reduce HIV Production in Elite Controllers

Identifieur interne : 000392 ( Pmc/Curation ); précédent : 000391; suivant : 000393

Plasmacytoid Dendritic Cells Reduce HIV Production in Elite Controllers

Auteurs : K. Machmach [Espagne] ; M. Leal [Espagne] ; C. Gras [France] ; P. Viciana [Espagne] ; M. Genebat [Espagne] ; E. Franco [Espagne] ; F. Boufassa ; O. Lambotte [France] ; J. P. Herbeuval [France] ; E. Ruiz-Mateos [Espagne]

Source :

RBID : PMC:3318617

Abstract

HIV elite controllers (EC) are a rare group of HIV-infected patients who are able to maintain undetectable viral loads during a long period of time in the absence of antiretroviral treatment. Adaptive immunity and host genetic factors, although implicated, do not entirely explain this phenomenon. On the other hand, plasmacytoid dendritic cells (pDCs) are the principal type I interferon (IFN) producers in response to viral infection, and it is unknown whether pDCs are involved in the control of HIV infection in EC. In our study, we analyzed peripheral pDC levels and IFN-α production by peripheral blood mononuclear cells (PBMCs) in EC compared to other groups of HIV-infected patients, the ability of pDCs to reduce HIV production in vitro, and the mechanisms potentially involved. We showed preserved pDC counts and IFN-α production in EC. We also observed a higher capacity of pDCs from EC to reduce HIV production and to induce T cell apoptosis, whereas pDCs from viremic patients barely responded without previous Toll-like receptor 9 (TLR-9) stimulus. The preserved functionality of pDCs from EC to reduce viral production may be one of the mechanisms involved in the control of HIV viremia in these subjects. These results demonstrate the importance of innate immunity in HIV pathogenesis, and an understanding of pDC mechanisms would be helpful for the design of new therapies.


Url:
DOI: 10.1128/JVI.07114-11
PubMed: 22318133
PubMed Central: 3318617

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F. Boufassa
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<p>HIV elite controllers (EC) are a rare group of HIV-infected patients who are able to maintain undetectable viral loads during a long period of time in the absence of antiretroviral treatment. Adaptive immunity and host genetic factors, although implicated, do not entirely explain this phenomenon. On the other hand, plasmacytoid dendritic cells (pDCs) are the principal type I interferon (IFN) producers in response to viral infection, and it is unknown whether pDCs are involved in the control of HIV infection in EC. In our study, we analyzed peripheral pDC levels and IFN-α production by peripheral blood mononuclear cells (PBMCs) in EC compared to other groups of HIV-infected patients, the ability of pDCs to reduce HIV production
<italic>in vitro</italic>
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<name>
<surname>Machmach</surname>
<given-names>K.</given-names>
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<xref ref-type="aff" rid="aff1">
<sup>a</sup>
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<xref ref-type="aff" rid="aff2">
<sup>b</sup>
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<given-names>M.</given-names>
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<sup>a</sup>
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<xref ref-type="aff" rid="aff2">
<sup>b</sup>
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<name>
<surname>Gras</surname>
<given-names>C.</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>c</sup>
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<name>
<surname>Viciana</surname>
<given-names>P.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
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<name>
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<given-names>M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
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<name>
<surname>Franco</surname>
<given-names>E.</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>d</sup>
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<name>
<surname>Boufassa</surname>
<given-names>F.</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>e</sup>
</xref>
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<name>
<surname>Lambotte</surname>
<given-names>O.</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>e</sup>
</xref>
<xref ref-type="aff" rid="aff6">
<sup>f</sup>
</xref>
<xref ref-type="aff" rid="aff7">
<sup>g</sup>
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<name>
<surname>Herbeuval</surname>
<given-names>J. P.</given-names>
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<xref ref-type="aff" rid="aff3">
<sup>c</sup>
</xref>
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<name>
<surname>Ruiz-Mateos</surname>
<given-names>E.</given-names>
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<xref ref-type="aff" rid="aff1">
<sup>a</sup>
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<xref ref-type="aff" rid="aff2">
<sup>b</sup>
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<aff id="aff1">
<label>a</label>
Laboratory of Immunovirology, Biomedicine Institute of Seville (IBIS), Infectious Diseases Service, Virgen del Rocío University Hospital, Seville, Spain</aff>
<aff id="aff2">
<label>b</label>
Biochemistry Department, Virgen del Rocío University Hospital, Seville, Spain</aff>
<aff id="aff3">
<label>c</label>
CNRS UMR 8147, Université Paris Descartes, Paris, France</aff>
<aff id="aff4">
<label>d</label>
Centro Regional de Transfusiones Sanguíneas Sevilla/Huelva y Banco de Tejidos, Seville, Spain</aff>
<aff id="aff5">
<label>e</label>
INSERM U1012, Bicêtre</aff>
<aff id="aff6">
<label>f</label>
AP-HP, Department of Internal Medicine and Infectious Diseases, Bicêtre Hospital, Bicêtre</aff>
<aff id="aff7">
<label>g</label>
Université Paris-Sud, U1012, Bicêtre, France</aff>
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<author-notes>
<corresp>Address correspondence to E. Ruiz-Mateos,
<email>ezequiel.ruizmateos@gmail.com</email>
.</corresp>
<fn fn-type="equal">
<p>J.P.H. and E.R.-M. contributed equally to this article.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<month>4</month>
<year>2012</year>
</pub-date>
<volume>86</volume>
<issue>8</issue>
<fpage>4245</fpage>
<lpage>4252</lpage>
<history>
<date date-type="received">
<day>22</day>
<month>12</month>
<year>2011</year>
</date>
<date date-type="accepted">
<day>29</day>
<month>1</month>
<year>2012</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2012, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv00812004245.pdf"></self-uri>
<abstract>
<p>HIV elite controllers (EC) are a rare group of HIV-infected patients who are able to maintain undetectable viral loads during a long period of time in the absence of antiretroviral treatment. Adaptive immunity and host genetic factors, although implicated, do not entirely explain this phenomenon. On the other hand, plasmacytoid dendritic cells (pDCs) are the principal type I interferon (IFN) producers in response to viral infection, and it is unknown whether pDCs are involved in the control of HIV infection in EC. In our study, we analyzed peripheral pDC levels and IFN-α production by peripheral blood mononuclear cells (PBMCs) in EC compared to other groups of HIV-infected patients, the ability of pDCs to reduce HIV production
<italic>in vitro</italic>
, and the mechanisms potentially involved. We showed preserved pDC counts and IFN-α production in EC. We also observed a higher capacity of pDCs from EC to reduce HIV production and to induce T cell apoptosis, whereas pDCs from viremic patients barely responded without previous Toll-like receptor 9 (TLR-9) stimulus. The preserved functionality of pDCs from EC to reduce viral production may be one of the mechanisms involved in the control of HIV viremia in these subjects. These results demonstrate the importance of innate immunity in HIV pathogenesis, and an understanding of pDC mechanisms would be helpful for the design of new therapies.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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