Distinct Immune Response in Two MERS-CoV-Infected Patients: Can We Go from Bench to Bedside?

被引:182
作者
Faure, Emmanuel [1 ]
Poissy, Julien [2 ,3 ]
Goffard, Anne [3 ,4 ]
Fournier, Clement [3 ,5 ]
Kipnis, Eric [1 ]
Titecat, Marie [3 ,6 ]
Bortolotti, Perinne [1 ]
Martinez, Laura [1 ]
Dubucquoi, Sylvain [3 ,6 ]
Dessein, Rodrigue [1 ]
Gosset, Philippe [7 ,8 ]
Mathieu, Daniel [2 ,3 ]
Guery, Benoit [1 ,7 ,8 ]
机构
[1] Univ Lille 2, Host Pathogen Translat Res Grp, Lille, France
[2] Univ Lille 2, Ctr Hosp Reg, Hop Roger Salengro, Pole Reanimat, Lille, France
[3] Univ Lille 2, Univ Lille, Lille, France
[4] Univ Lille 2, Ctr Hosp Reg, Ctr Biol Pathol, Lab Virol, Lille, France
[5] Univ Lille 2, Ctr Hosp Reg, Clin Malad Resp Endoscopie Bronch & Pleurale Endo, Lille, France
[6] Univ Lille 2, Ctr Hosp Reg, Ctr Biol Pathol, Inst Microbiol, Lille, France
[7] Ctr Natl Rech Sci, Unite Mixte Rech 8204, Lille, France
[8] Inst Natl Sante & Rech Med, U1019, Lille, France
来源
PLOS ONE | 2014年 / 9卷 / 02期
关键词
RESPIRATORY SYNDROME CORONAVIRUS; INNATE; INTERFERON; REPLICATION;
D O I
10.1371/journal.pone.0088716
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFN alpha, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFN alpha, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFN gamma that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFN alpha in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNa treatment during MERS-CoV infection.
引用
收藏
页数:7
相关论文
共 23 条
[1]  
[Anonymous], P NATL ACAD SCI US
[2]   Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study [J].
Assiri, Abdullah ;
Al-Tawfiq, Jaffar A. ;
Al-Rabeeah, Abdullah A. ;
Al-Rabiah, Fahad A. ;
Al-Hajjar, Sami ;
Al-Barrak, Ali ;
Flemban, Hesham ;
Al-Nassir, Wafa N. ;
Balkhy, Hanan H. ;
Al-Hakeem, Rafat F. ;
Makhdoom, Hatem Q. ;
Zumla, Alimuddin I. ;
Memish, Ziad A. .
LANCET INFECTIOUS DISEASES, 2013, 13 (09) :752-761
[3]   Beyond pattern recognition: five immune checkpoints for scaling the microbial threat [J].
Blander, J. Magarian ;
Sander, Leif E. .
NATURE REVIEWS IMMUNOLOGY, 2012, 12 (03) :215-225
[4]   Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome [J].
Cameron, Mark J. ;
Ran, Longsi ;
Xu, Luoling ;
Danesh, Ali ;
Bermejo-Martin, Jesus F. ;
Cameron, Cheryl M. ;
Muller, Matthew P. ;
Gold, Wayne L. ;
Richardson, Susan E. ;
Poutanen, Susan M. ;
Willey, Barbara M. ;
DeVries, Mark E. ;
Fang, Yuan ;
Seneviratne, Charit ;
Bosinger, Steven E. ;
Persad, Desmond ;
Wilkinson, Peter ;
Greller, Larry D. ;
Somogyi, Roland ;
Humar, Atul ;
Keshavjee, Shaf ;
Louie, Marie ;
Loeb, Mark B. ;
Brunton, James ;
McGeer, Allison J. ;
Kelvin, David J. .
JOURNAL OF VIROLOGY, 2007, 81 (16) :8692-8706
[5]   MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment [J].
de Wilde, Adriaan H. ;
Raj, V. Stalin ;
Oudshoorn, Diede ;
Bestebroer, Theo M. ;
van Nieuwkoop, Stefan ;
Limpens, Ronald W. A. L. ;
Posthuma, Clara C. ;
van der Meer, Yvonne ;
Barcena, Montserrat ;
Haagmans, Bart L. ;
Snijder, Eric J. ;
van den Hoogen, Bernadette G. .
JOURNAL OF GENERAL VIROLOGY, 2013, 94 :1749-1760
[6]   SARS coronavirus and innate immunity [J].
Frieman, Matthew ;
Heise, Mark ;
Baric, Ralph .
VIRUS RESEARCH, 2008, 133 (01) :101-112
[7]   Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission [J].
Guery, Benoit ;
Poissy, Julien ;
el Mansouf, Loubna ;
Sejourne, Caroline ;
Ettahar, Nicolas ;
Lemaire, Xavier ;
Vuotto, Fanny ;
Goffard, Anne ;
Behillil, Sylvie ;
Enouf, Vincent ;
Caro, Valerie ;
Mailles, Alexandra ;
Che, Didier ;
Manuguerra, Jean-Claude ;
Mathieu, Daniel ;
Fontanet, Arnaud ;
van der Werf, Sylvie .
LANCET, 2013, 381 (9885) :2265-2272
[8]   Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus [J].
Josset, Laurence ;
Menachery, Vineet D. ;
Gralinski, Lisa E. ;
Agnihothram, Sudhakar ;
Sova, Pavel ;
Carter, Victoria S. ;
Yount, Boyd L. ;
Graham, Rachel L. ;
Baric, Ralph S. ;
Katze, Michael G. .
MBIO, 2013, 4 (03)
[9]   Viruses and interferon: A fight for supremacy [J].
Katze, MG ;
He, YP ;
Gale, M .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (09) :675-687
[10]   Th17 cell based vaccines in mucosal immunity [J].
Kumar, Pawan ;
Chen, Kong ;
Kolls, Jay K. .
CURRENT OPINION IN IMMUNOLOGY, 2013, 25 (03) :373-380