E Doyle

J Boucau

JJ Chang

M Altfeld

M Griesbeck

RJ Lindsay

S LeGall

Retrovirology

PubMed

Crossref

POSTER PRESENTATION Open AccessImplications of post-translational modifications ofIRF7 on pDC IFN-alpha responseM Griesbeck*, E Doyle, RJ Lindsay, J Boucau, S LeGall, M Altfeld, JJ ChangFrom AIDS Vaccine 2012Boston, MA, USA. 9-12 September 2012BackgroundWe previously showed that plasmacytoid dendritic cells(pDCs) derived from females can produce significantlymore IFN-alpha in response to HIV-1 and HIV-1-encodedTLR7/8 ligands than pDCs derived from males, resultingin stronger secondary activation of CD8+ T cells (Meieret al., Nat Med 2009). Given the crucial role of interferonregulatory factor 7 (IRF7) in the regulation of type I IFNproduction by pDCs, the goal of the current study was toinvestigate its impact on the observed differences.MethodsFresh PBMC were isolated from HIV-1-negative subjectsenrolled at Massachusetts General Hospital and stimu-lated by either CL097 (synthetic TLR7 ligand) or AT-2inactivated HIV-1. Phosphorylation levels of proteinsinvolved in the TLR7 pathway including IRF7 were mea-sured in pDCs by phospho-flow cytometry at baselineand at different time-points after TLR7 stimulation. Thekinetics of IRF7 modifications in the TLR7 pathwaywere confirmed using mRNA expression of IFN-alpha.ResultsBaseline levels of phosphorylated IRF7 were found to besimilar between males and females. However weobserved faster phosphorylation kinetics of IRF7 infemales than in males using flow cytometry with phos-pho-IRF7 peaking in females at 20min post-stimulationand males at 30min.ConclusionThese data indicate that sex differences in the kinetics ofIRF7 phosphorylation might account for described higherIFN-alpha production upon TLR7 stimulation in females,providing new insights into the mechanisms underlyingfaster HIV-1 disease progression in females compared tomales after controlling for viral load (Farzadegan et al.,Lancet 1998).Published: 13 September 2012doi:10.1186/1742-4690-9-S2-P176Cite this article as: Griesbeck et al.: Implications of post-translationalmodifications of IRF7 on pDC IFN-alpha response. Retrovirology 2012 9(Suppl 2):P176.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitRagon Institute of MGH, MIT and Harvard, Charlestown, MA, USAGriesbeck et al. Retrovirology 2012, 9(Suppl 2):P176http://www.retrovirology.com/content/9/S2/P176© 2012 Griesbeck et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

Implications of post-translational modifications of IRF7 on pDC IFN-alpha response

Springer - Publisher Connector

POSTER PRESENTATION Open Access
Implications of post-translational modifications of
IRF7 on pDC IFN-alpha response
M Griesbeck*, E Doyle, RJ Lindsay, J Boucau, S LeGall, M Altfeld, JJ Chang
From AIDS Vaccine 2012
Boston, MA, USA. 9-12 September 2012
Background
We previously showed that plasmacytoid dendritic cells
(pDCs) derived from females can produce significantly
more IFN-alpha in response to HIV-1 and HIV-1-encoded
TLR7/8 ligands than pDCs derived from males, resulting
in stronger secondary activation of CD8+ T cells (Meier
et al., Nat Med 2009). Given the crucial role of interferon
regulatory factor 7 (IRF7) in the regulation of type I IFN
production by pDCs, the goal of the current study was to
investigate its impact on the observed differences.
Methods
Fresh PBMC were isolated from HIV-1-negative subjects
enrolled at Massachusetts General Hospital and stimu-
lated by either CL097 (synthetic TLR7 ligand) or AT-2
inactivated HIV-1. Phosphorylation levels of proteins
involved in the TLR7 pathway including IRF7 were mea-
sured in pDCs by phospho-flow cytometry at baseline
and at different time-points after TLR7 stimulation. The
kinetics of IRF7 modifications in the TLR7 pathway
were confirmed using mRNA expression of IFN-alpha.
Results
Baseline levels of phosphorylated IRF7 were found to be
similar between males and females. However we
observed faster phosphorylation kinetics of IRF7 in
females than in males using flow cytometry with phos-
pho-IRF7 peaking in females at 20min post-stimulation
and males at 30min.
Conclusion
These data indicate that sex differences in the kinetics of
IRF7 phosphorylation might account for described higher
IFN-alpha production upon TLR7 stimulation in females,
providing new insights into the mechanisms underlying
faster HIV-1 disease progression in females compared to
males after controlling for viral load (Farzadegan et al.,
Lancet 1998).
Published: 13 September 2012
doi:10.1186/1742-4690-9-S2-P176
Cite this article as: Griesbeck et al.: Implications of post-translational
modifications of IRF7 on pDC IFN-alpha response. Retrovirology 2012 9
(Suppl 2):P176.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Ragon Institute of MGH, MIT and Harvard, Charlestown, MA, USA
Griesbeck et al. Retrovirology 2012, 9(Suppl 2):P176
http://www.retrovirology.com/content/9/S2/P176
© 2012 Griesbeck 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.


https://retrovirology.biomedcentral.com/track/pdf/10.1186/1742-4690-9-S2-P176?site=retrovirology.biomedcentral.com

Implications of post-translational modifications of IRF7 on pDC IFN-alpha response

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