Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells.
Plasmacytoid dendritic cells (pDCs) play essential roles in directing immune responses. These cells may be particularly important in determining the nature of immune responses to viral infections in patients with allergic asthma as well those with other atopic diseases. The purposes of this study were 1) to compare the functional capacity of pDCs in patients with one type of allergic disorder, allergic asthma, and controls; 2) to determine whether IgE cross-linking affects antiviral responses of influenza-exposed pDCs; and 3) to determine whether evidence of counterregulation of FcepsilonRIalpha and IFN-alpha pathways exists in these cells. pDC function was assessed in a subset of asthma patients and in controls by measuring IFN-alpha production after exposure of purified pDCs to influenza viruses. FcepsilonRIalpha expression on pDCs was determined by flow cytometry in blood samples from patients with allergic asthma and controls. pDCs from patients with asthma secreted significantly less IFN-alpha upon exposure to influenza A (572 versus 2815; p = 0.03), and secretion was inversely correlated with serum IgE levels. Moreover, IgE cross-linking prior to viral challenge resulted in 1) abrogation of the influenza-induced pDC IFN-alpha response; 2) diminished influenza and gardiquimod-induced TLR-7 upregulation in pDCs; and 3) interruption of influenza-induced upregulation of pDC maturation/costimulatory molecules. In addition, exposure to influenza and gardiquimod resulted in upregulation of TLR-7, with concomitant downregulation of FcepsilonRIalpha expression in pDCs. These data suggest that counterregulation of FcepsilonRI and TLR-7 pathways exists in pDCs, and that IgE cross-linking impairs pDC antiviral responses.
Gill
Michelle A
MA
Division of Allergy and Immunology, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas and Children's Medical Center Dallas, Dallas, TX 75290, USA. michelle.gill@utsouthwestern.edu
Bajwa
Gagan
G
George
Tiffany A
TA
Dong
Caroline C
CC
Dougherty
Irene I
II
Jiang
Nan
N
Gan
Vanthaya N
VN
Gruchalla
Rebecca S
RS
D000293:Adolescent; D000328:Adult; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D017455:Receptors, IgE / Q000096:biosynthesis / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology; D055815:Young Adult
C543355:FcepsilonRI alpha-chain, human; D016898:Interferon-alpha; D017455:Receptors, IgE; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D007073:Immunoglobulin E
Nature. 1998 Mar 19;392(6673):245-52
9521319
Science. 2004 Mar 5;303(5663):1526-9
14976262
J Immunol. 2005 Nov 1;175(9):5724-31
16237063
J Pediatr. 2003 Feb;142(2 Suppl):S9-13; discussion S13-4
12584514
Clin Exp Allergy. 2006 Mar;36(3):331-7
16499644
Int Arch Allergy Immunol. 2002 Jan;127(1):82-8
11893858
J Clin Invest. 2003 Apr;111(7):1047-56
12671054
J Allergy Clin Immunol. 2008 Feb;121(2):486-91
18036648
J Immunol. 1998 Sep 15;161(6):2731-9
9743330
Nat Immunol. 2000 Oct;1(4):305-10
11017101
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5598-603
15034168
J Allergy Clin Immunol. 2003 Dec;112(6):1132-8
14657872
J Clin Virol. 2005 Nov;34(3):161-9
16126001
Annu Rev Immunol. 2000;18:767-811
10837075
J Allergy Clin Immunol. 2003 Mar;111(3 Suppl):S799-804
12618746
J Immunol. 2000 Oct 1;165(7):4062-8
11034417
J Allergy Clin Immunol. 2003 Dec;112(6):1147-54
14657874
Nat Immunol. 2004 Dec;5(12):1219-26
15549123
Hum Immunol. 2002 Dec;63(12):1126-32
12480256
Annu Rev Immunol. 2005;23:275-306
15771572
Clin Exp Allergy. 2008 May;38(5):781-8
18318750
Pediatr Infect Dis J. 2005 Nov;24(11 Suppl):S170-6, discussion S174-5
16378042
J Immunol. 2005 Feb 15;174(4):2396-403
15699176
J Allergy Clin Immunol. 2005 Apr;115(4):668-74; quiz 675
15805982
Clin Exp Allergy. 2005 Sep;35(9):1125-34
16164437
J Allergy Clin Immunol. 2006 Aug;118(2):331-6
16890754
Curr Allergy Asthma Rep. 2004 Jul;4(4):263-9
15175139
Science. 2004 Mar 5;303(5663):1529-31
14976261
J Allergy Clin Immunol. 2003 Jan;111(1):38-44
12532094
J Exp Med. 2006 Jun 12;203(6):1399-405
16735691