Increased adaptive immune responses and proper feedback regulation protect against clinical dengue

被引:64
作者
Simon-Loriere, Etienne [1 ,2 ]
Duong, Veasna [3 ]
Tawfik, Ahmed [1 ,2 ]
Ung, Sivlin [4 ]
Ly, Sowath [5 ]
Casademont, Isabelle [1 ,2 ]
Prot, Matthieu [1 ,2 ]
Courtejoie, Noemie [1 ,2 ]
Bleakley, Kevin [6 ,7 ]
Buchy, Philippe [3 ]
Tarantola, Arnaud [5 ]
Dussart, Philippe [3 ,8 ]
Cantaert, Tineke [4 ,8 ]
Sakuntabhai, Anavaj [1 ,2 ]
机构
[1] Inst Pasteur, Dept Genomes & Genet, Funct Genet Infect Dis Unit, F-75015 Paris, France
[2] CNRS, Unite Rech Associee 3012, F-75015 Paris, France
[3] Int Network Pasteur Inst, Inst Pasteur Cambodge, Virol Unit, Phnom Penh 12201, Cambodia
[4] Int Network Pasteur Inst, Inst Pasteur Cambodge, Immunol Grp, Phnom Penh 12201, Cambodia
[5] Int Network Pasteur Inst, Inst Pasteur Cambodge, Epidemiol & Publ Hlth Unit, Phnom Penh 12201, Cambodia
[6] INRIA Saclay, F-91120 Palaiseau, France
[7] Dept Math Orsay, F-91400 Orsay, France
[8] GlaxoSmithKline GSK Vaccines, Singapore 637421, Singapore
关键词
ORIGINAL ANTIGENIC SIN; VIRUS-INFECTION; CELL RESPONSES; TIME-INTERVAL; CHILDREN; INAPPARENT; NS3; DETERMINANTS; MEMBERS; BURDEN;
D O I
10.1126/scitranslmed.aal5088
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Clinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on an individual's health. We used an integrated approach of transcriptional profiling and immunological analysis to compare a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune response pathways were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T cell and B cell activation pathways was differentially regulated, independent of viral load and previous DENV infection history. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals, as demonstrated by increased activation of T cell apoptosis-related pathways and Fc gamma RIIB (Fc gamma receptor IIB) signaling associated with decreased anti-DENV-specific antibody concentrations. Together, our data illustrate that symptom-free DENV infection in children is associated with increased activation of the adaptive immune compartment and proper control mechanisms, leading to elimination of viral infection without excessive immune activation, with implications for novel vaccine development strategies.
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页数:13
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共 58 条
  • [31] LIVINGSTON PG, 1995, J IMMUNOL, V154, P1287
  • [32] Understanding the contribution of cellular immunity to dengue disease pathogenesis
    Mathew, Anuja
    Rothman, Alan L.
    [J]. IMMUNOLOGICAL REVIEWS, 2008, 225 : 300 - 313
  • [33] Mongkolsapaya J, 2003, NAT MED, V9, P921, DOI 10.1038/nm887
  • [34] Symptomatic Versus Inapparent Outcome in Repeat Dengue Virus Infections Is Influenced by the Time Interval between Infections and Study Year
    Montoya, Magelda
    Gresh, Lionel
    Carlos Mercado, Juan
    Williams, Katherine L.
    Jose Vargas, Maria
    Gutierrez, Gamaliel
    Kuan, Guillermina
    Gordon, Aubree
    Balmaseda, Angel
    Harris, Eva
    [J]. PLOS NEGLECTED TROPICAL DISEASES, 2013, 7 (08):
  • [35] NFAT, immunity and cancer: a transcription factor comes of age
    Mueller, Martin R.
    Rao, Anjana
    [J]. NATURE REVIEWS IMMUNOLOGY, 2010, 10 (09) : 645 - 656
  • [36] Immune Response to Dengue Virus and Prospects for a Vaccine
    Murphy, Brian R.
    Whitehead, Stephen S.
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 2011, 29 : 587 - 619
  • [37] Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection
    Ngono, Annie Elong
    Chen, Hui-Wen
    Tang, William W.
    Joo, Yunichel
    King, Kevin
    Weiskopf, Daniela
    Sidney, John
    Sette, Alessandro
    Shresta, Sujan
    [J]. EBIOMEDICINE, 2016, 13 : 284 - 293
  • [38] Temporal Dynamics of the Transcriptional Response to Dengue Virus Infection in Nicaraguan Children
    Popper, Stephen J.
    Gordon, Aubree
    Liu, Minghsun
    Balmaseda, Angel
    Harris, Eva
    Relman, David A.
    [J]. PLOS NEGLECTED TROPICAL DISEASES, 2012, 6 (12):
  • [39] B Cell Responses during Secondary Dengue Virus Infection Are Dominated by Highly Cross-Reactive, Memory-Derived Plasmablasts
    Priyamvada, Lalita
    Cho, Alice
    Onlamoon, Nattawat
    Zheng, Nai-Ying
    Huang, Min
    Kovalenkov, Yevgeniy
    Chokephaibulkit, Kulkanya
    Angkasekwinai, Nasikarn
    Pattanapanyasat, Kovit
    Ahmed, Rafi
    Wilson, Patrick C.
    Wrammert, Jens
    [J]. JOURNAL OF VIROLOGY, 2016, 90 (12) : 5574 - 5585
  • [40] limma powers differential expression analyses for RNA-sequencing and microarray studies
    Ritchie, Matthew E.
    Phipson, Belinda
    Wu, Di
    Hu, Yifang
    Law, Charity W.
    Shi, Wei
    Smyth, Gordon K.
    [J]. NUCLEIC ACIDS RESEARCH, 2015, 43 (07) : e47