Sex Differences in TNFAIP3 Levels in pDC upon TLR7 Stimulation

AIDS Research and Human RetrovirusesVol. 30, No. S1 Innate ImmunityFree AccessSex Differences in TNFAIP3 Levels in pDC upon TLR7 StimulationSusanne M. Ziegler, Morgane Griesbeck, Judy Chang, and Marcus AltfeldSusanne M. ZieglerHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Viral Immunology, Hamburg, GermanySearch for more papers by this author, Morgane GriesbeckRagon Institute of MIT, MGH and Harvard, Boston, MA, United StatesCIMI/ U1135, Paris, FranceSearch for more papers by this author, Judy ChangMonash University, Department of Infectious Diseases, Melbourne, AustraliaSearch for more papers by this author, and Marcus AltfeldHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Viral Immunology, Hamburg, GermanyRagon Institute of MIT, MGH and Harvard, Boston, MA, United StatesSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5255.abstractAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail P12.16Background: The outcomes of many diseases differ between women and men. It is well documented that women have a higher incidence as well as more severe pathogenesis of autoimmune diseases. Furthermore, accumulating evidence indicates a role of sex-based divergence of infectious diseases, including influenza and HIV-1. In HIV-1 infection, clinical studies have shown faster disease progression and stronger immune activation in females compared to males for the same level of viral replication, as well as better control of initial viremia in women during primary infection (Meier et al. 2009 Nat Med, Sterling et al. 2001 NEJM, Farzadegan et al. 1998 Lancet). It has been suggested that this is mainly due to Toll-like receptor (TLR)-mediated responses of plasmacytoid dendritic cells (pDCs), the main producers of IFN-α. We investigated the role of the TNF-α induced protein (TNFAIP) 3 (A20), an estrogen-regulated early NF-κB-responsive gene that encodes a ubiquitin-editing protein involved in negative feedback regulation of NF-κB signaling. Thus, TNFAIP3 is known to be a potent anti-inflammatory signaling molecule that restricts multiple intracellular signaling cascades including TLR signaling.Methods: 100 pDC were sorted and stimulated for 2h with a TLR7 ligand. Using fluidigm technology the expression level of TNFAIP3 mRNA was determined.Results: We detected a significant difference in TNFAIP3 mRNA upregulation in pDCs after 2h TLR7 stimulation between males and females (p<0.05). pDCs from males showed a 2-log higher expression level of TNFAIP3 mRNA compared to females, associated with lower production of IFN-α in pDCs from males in response to HIV-1-derived TLR7 ligands and HIV-1.Conclusions: Taken together, these data demonstrate that sex differences described in response to HIV-1 are associated with the enhanced expression of the sex hormone-dependent inhibitory regulator of TLR signaling TNFAIP3 in pDCs of men compared to women, providing a novel target to modulate the inflammatory IFN-α response to HIV-1.FiguresReferencesRelatedDetails Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Susanne M. Ziegler, Morgane Griesbeck, Judy Chang, and Marcus Altfeld.Sex Differences in TNFAIP3 Levels in pDC upon TLR7 Stimulation.AIDS Research and Human Retroviruses.Oct 2014.A129-A130.http://doi.org/10.1089/aid.2014.5255.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download