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HIV triggers immunoregulatory dendritic cells and regulatory T cells through the non-canonical NF-kB pathway

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HAL Id: inserm-00731775

https://www.hal.inserm.fr/inserm-00731775

Submitted on 13 Sep 2012

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HIV triggers immunoregulatory dendritic cells and

regulatory T cells through the non-canonical NF-kB

pathway

Olivier Manches, Melissa Victoria Fernandez, Joël Plumas, Laurence

Chaperot, Nina Bhardwaj

To cite this version:

Olivier Manches, Melissa Victoria Fernandez, Joël Plumas, Laurence Chaperot, Nina Bhardwaj. HIV

triggers immunoregulatory dendritic cells and regulatory T cells through the non-canonical NF-kB

pathway. Retrovirology, BioMed Central, 2012, 9 (Suppl 2), pp.P184. �inserm-00731775�

(2)

P O S T E R P R E S E N T A T I O N

Open Access

HIV triggers immunoregulatory dendritic cells

and regulatory T cells through the non-canonical

NF-kB pathway

O Manches

1*

, MV Fernandez

1

, J Plumas

2

, L Chaperot

2

, N Bhardwaj

1

From

AIDS Vaccine 2012

Boston, MA, USA. 9-12 September 2012

Background

HIV stimulates plasmacytoid dendritic cell (pDC) through TLR7 and induce the secretion of high levels of IFNa. pDC stimulated by HIV also upregulate the expression of the enzyme indoleamine 2,3 dioxygenase (IDO). IDO is critical for the induction of regulatory T cells (Treg) by HIV-activated pDC. We investigated the molecular mechanisms of IDO induction and its consequences for Treg function.

Methods

The cells used were purified primary pDC and the GEN pDC cell line. A combination of siRNA knock-down, immunoprecipitation of TLR signaling pathway molecules, IDO promoter engineering and chromatin immunopreci-pitation was used to determine the molecular mechanisms of IDO induction in pDC. To analyze Treg function and interaction with conventional DC (cDC), blocking antibo-dies to CTLA- 4 and CTLA-4-Ig were used.

Results

We demonstrate that HIV induces activation of the non-canonical NF-kB pathway in pDC, and is essential for IDO induction. TLR7 triggering induces recruitment of TRAF3 to the TLR-MyD88 complex, followed by release of NIK and phosphorylation of IKKa. Activation of the non-canonical NF-B pathway culminates in p52/RelB nuclear translocation and binding to the IDO promoter.

Furthermore, IDO-expressing pDC trigger the genera-tion of Treg, which dampen cDC activagenera-tion through CTLA-4. CTLA-4 also induces IDO expression in cDC

in a NIK-dependent fashion, allowing cDC to induce Treg from naïve CD4+ T cells.

Conclusion

The non-canonical NF-kB pathway plays a central role in regulating IDO expression in pDC and cDC upon HIV infection, and may be a potential target for regulating Treg activity in chronic or acute HIV infection.

Author details

1NYU Cancer Institute, New York City, NY, USA.2Inserm, U823,

Immunobiologie et Immunotherapie des Cancers, La Tronche, France. Published: 13 September 2012

doi:10.1186/1742-4690-9-S2-P184

Cite this article as:Manches et al.: HIV triggers immunoregulatory dendritic cells and regulatory T cells through the non-canonical NF-kB pathway. Retrovirology2012 9(Suppl 2):P184.

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1NYU Cancer Institute, New York City, NY, USA

Full list of author information is available at the end of the article Manches et al. Retrovirology 2012, 9(Suppl 2):P184 http://www.retrovirology.com/content/9/S2/P184

© 2012 Manches et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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