Estrogen inhibits dendritic cell maturation to RNA viruses.
Dendritic cells (DCs) play a central role in initiating and polarizing the immune response. Therefore, DC maturation represents a key control point in the shift from innate to adaptive immunity. It is suspected that during pregnancy, hormones are critical factors that modulate changes reported to occur in maternal immunity. Here we examined the effect of 17-beta-estradiol (E2) on the maturational response triggered by virus in human DCs and its influence on their ability to activate naive T cells. We developed an in vitro system to measure the response of DCs to virus infection with Newcastle disease virus (NDV) after a 24-hour E2 treatment. Using this system, we demonstrated that E2 pretreatment down-regulated the antiviral response to RNA viruses in DCs by profoundly suppressing type I interferon (IFN) synthesis and other important inflammatory products. In addition, the DCs capacity to stimulate naive CD4 T cells was also reduced. These results suggest an important role for E2 in suppressing the antiviral response and provide a mechanism for the reduced immunity to virus infection observed during pregnancy.
Escribese
Maria M
MM
Department of Microbiology, The Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Kraus
Thomas
T
Rhee
Esther
E
Fernandez-Sesma
Ana
A
López
Carolina B
CB
Moran
Thomas M
TM
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics / Q000494:pharmacology; D009522:Newcastle disease virus / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012327:RNA Virus Infections / Q000276:immunology; D012328:RNA Viruses / Q000276:immunology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists / Q000037:antagonists & inhibitors
D004967:Estrogens; D011960:Receptors, Estrogen; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
J Immunol. 2007 Feb 15;178(4):2572-8
17277167
Virology. 2002 Nov 10;303(1):33-46
12482656
J Invest Dermatol. 1995 Jul;105(1 Suppl):14S-19S
7615991
Science. 1999 Feb 26;283(5406):1277-8
10084932
J Virol. 2006 Apr;80(7):3128-34
16537581
Scand J Clin Lab Invest. 2007;67(5):519-25
17763188
Blood. 2004 Sep 1;104(5):1404-10
15142882
J Neuroendocrinol. 2008 Apr;20(4):462-9
18266939
Curr Opin Obstet Gynecol. 2007 Apr;19(2):120-5
17353679
Public Health Rep. 1986 Mar-Apr;101(2):205-11
3083477
J Virol. 2003 Sep;77(17):9522-32
12915566
J Immunol. 2005 Sep 1;175(5):2851-8
16116171
J Immunol. 2008 Jan 1;180(1):630-6
18097065
J Immunol. 2005 Nov 1;175(9):5716-23
16237062
J Immunol. 2004 Feb 1;172(3):1426-36
14734718
J Infect Dis. 2007 Apr 1;195(7):1062-70
17330798
J Immunol. 2008 Feb 15;180(4):2679-85
18250480
J Neuroimmunol. 2004 Nov;156(1-2):58-65
15465596
Emerg Infect Dis. 2008 Jan;14(1):95-100
18258087
Mediators Inflamm. 2006;2006(4):30485
17047289
Immunity. 2007 Aug;27(2):240-52
17723216
Immunobiology. 2006;211(6-8):627-32
16920501
Nat Immunol. 2004 Jul;5(7):730-7
15208624
Immunol Res. 2005;31(2):91-106
15778508
FEMS Immunol Med Microbiol. 2003 Aug 18;38(1):13-22
12900050
Virology. 1998 Dec 20;252(2):324-30
9878611
Infect Dis Clin North Am. 2007 Sep;21(3):601-15, vii
17826614
Int Arch Allergy Immunol. 2004 Jul;134(3):179-85
15178886
Reprod Biol Endocrinol. 2003 Feb 6;1:13
12646062
Am J Obstet Gynecol. 1958 Oct;76(4):897-902
13583035
J Exp Med. 2005 May 2;201(9):1435-46
15851485
J Virol. 2006 Jul;80(13):6295-304
16775317
J Neurosci. 2003 Oct 1;23(26):8836-43
14523084
J Gastroenterol Hepatol. 2007 May;22(5):676-82
17444855
Clin Immunol. 2004 Dec;113(3):224-30
15507385
Immunity. 2005 Jul;23(1):19-28
16039576
J Infect Dis. 2003 Apr 1;187(7):1126-36
12660927
Am J Pathol. 2003 Oct;163(4):1313-20
14507640
J Immunol. 2006 Oct 1;177(7):4503-13
16982887
J Interferon Cytokine Res. 2001 Sep;21(9):763-73
11576470
Immunol Rev. 2007 Dec;220:214-24
17979849
Eur J Obstet Gynecol Reprod Biol. 1999 Apr;83(2):137-42
10391522
Oncogene. 2008 Jan 7;27(2):181-9
18176599
Autoimmunity. 2007 Sep;40(6):470-81
17729041
Am J Obstet Gynecol. 1959 Dec;78:1172-5
13824729
J Virol. 2007 Jul;81(13):7316-9
17475649
J Interferon Cytokine Res. 2005 Dec;25(12):788-98
16375607
J Immunol. 2005 Oct 15;175(8):5050-7
16210608
Nucleic Acids Res. 2002 May 15;30(10):e48
12000853