Impaired type I and III interferon response to rhinovirus infection during pregnancy and asthma

被引:60
作者
Forbes, Rebecca Louise [1 ,2 ]
Gibson, Peter G. [1 ,2 ,3 ]
Murphy, Vanessa E. [1 ,2 ]
Wark, Peter A. B. [3 ]
机构
[1] Univ Newcastle, Ctr Asthma & Resp Dis, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia
[2] Hunter Med Res Inst, Newcastle, NSW 2300, Australia
[3] John Hunter Hosp, Dept Resp & Sleep Med, New Lambton, NSW 2350, Australia
基金
英国医学研究理事会;
关键词
PLASMACYTOID DENDRITIC CELL; BRONCHIAL EPITHELIAL-CELLS; RESPIRATORY ILLNESS; LAMBDA-INTERFERONS; IMMUNE-RESPONSES; VIRAL-INFECTION; IFN-ALPHA/BETA; INFLUENZA; HOSPITALIZATIONS; EXACERBATIONS;
D O I
10.1136/thoraxjnl-2011-200708
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background Acute respiratory tract infections are common ailments to all individuals and the human rhinoviruses (HRVs) cause most of these infections. Pregnant women have increased susceptibility and disease severity to viral infections like influenza and HRVs, as do asthmatics. Successful pregnancy requires immunological modulation to permit fetal tolerance. Objectives To determine whether pregnant women have reduced innate antiviral interferon (IFN) responses to HRV infection compared with non-pregnant women. Methods An in vitro culture system was used, where peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of 54 women, including 10 stable asthmatics who were pregnant and 10 who were not pregnant, 10 non-asthmatic women who were pregnant, 10 who were >= 6 months post partum and 10 who were not pregnant. Samples were also collected from four exacerbating pregnant asthmatics. PBMCs were cultured with HRV43 and HRV1B. The antiviral proteins IFN alpha and IFN lambda were measured from culture supernatants by ELISA. Results Compared with healthy non-pregnant women, pregnant women had significantly reduced innate IFN responses to HRV infection (p<0.02), persisting >= 6 months post partum (p <= 0.02). Pregnant asthmatics had significantly reduced IFN lambda responses compared with healthy non-pregnant women (p <= 0.034), while during current asthma exacerbations a decrease in IFN alpha (p <= 0.023) and IFN lambda (p=0.007) was observed. Induction by a TLR7 agonist induced a similar pattern of decreased innate IFNs during pregnancy as observed when HRV was the inducing agent. Conclusions Reduced antiviral IFNs during pregnancy and asthma provide an important mechanism for increased susceptibility, morbidity and mortality in pregnant women with respiratory viral infection.
引用
收藏
页码:209 / 214
页数:6
相关论文
共 33 条
[1]   IFN-λ:: Novel antiviral cytokines [J].
Ank, Nina ;
West, Hans ;
Paludan, Soren R. .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2006, 26 (06) :373-379
[2]  
[Anonymous], ASTHMA AUSTR FINDING
[3]   Maternal circulating interferon-γ and interleukin-6 as biomarkers of Th1/Th2 immune status throughout pregnancy [J].
Aris, Aziz ;
Lambert, Frederic ;
Bessette, Paul ;
Moutquin, Jean-Marie .
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH, 2008, 34 (01) :7-11
[4]   Transcriptional networks in plasmacytoid dendritic cells stimulated with synthetic TLR 7 agonists [J].
Birmachu, Woubalem ;
Gleason, Raymond M. ;
Bulbulian, Barbara J. ;
Riter, Christie L. ;
Vasilakos, John P. ;
Lipson, Kenneth E. ;
Nikolsky, Yuri .
BMC IMMUNOLOGY, 2007, 8 (1) :1-U18
[5]   Role of early cytokines, including alpha and beta interferons (IFN-α/β), in innate and adaptive immune responses to viral infections [J].
Biron, CA .
SEMINARS IN IMMUNOLOGY, 1998, 10 (05) :383-390
[6]   Viral infection and Toll-like receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocyte-derived dendritic cells [J].
Coccia, EM ;
Severa, M ;
Giacomini, E ;
Monneron, D ;
Remoli, ME ;
Julkunen, I ;
Cella, M ;
Lande, R ;
Uzé, G .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (03) :796-805
[7]   Role of deficient type III interferon-λ production in asthma exacerbations [J].
Contoli, Marco ;
Message, Simon D. ;
Laza-Stanca, Vasile ;
Edwards, Michael R. ;
Wark, Peter A. B. ;
Bartlett, Nathan W. ;
Kebadze, Tatiana ;
Mallia, Patrick ;
Stanciu, Luminita A. ;
Parker, Hayley L. ;
Slater, Louise ;
Lewis-Antes, Anita ;
Kon, Onn M. ;
Holgate, Stephen T. ;
Davies, Donna E. ;
Kotenko, Sergei V. ;
Papi, Alberto ;
Johnston, Sebastian L. .
NATURE MEDICINE, 2006, 12 (09) :1023-1026
[8]   Hospitalizations with respiratory illness among pregnant women during influenza season [J].
Cox, Shanna ;
Posner, Samuel F. ;
McPheeters, Melissa ;
Jamieson, Denise J. ;
Kourtis, Athena P. ;
Meikle, Susan .
OBSTETRICS AND GYNECOLOGY, 2006, 107 (06) :1315-1322
[9]   Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women [J].
Dodds, Linda ;
McNeil, Shelly A. ;
Fell, Deshayne B. ;
Allen, Victoria M. ;
Coombs, Ann ;
Scott, Jeffrey ;
MacDonald, Noni .
CANADIAN MEDICAL ASSOCIATION JOURNAL, 2007, 176 (04) :463-468
[10]   PS power and sample size program available for free on the Internet [J].
Dupont, WD ;
Plummer, WD .
CONTROLLED CLINICAL TRIALS, 1997, 18 (03) :274-274