Decoding Susceptibility to Respiratory Viral Infections and Asthma Inception in Children.
Decoding Susceptibility to Respiratory Viral Infections and Asthma Inception in Children.
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解码儿童对呼吸道病毒感染和哮喘的易感性。
DOI：
10.3390/ijms21176372
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发表时间：
2020-09-02
影响因子：
5.6
通讯作者：
Bosco A
中科院分区：
文献类型：
--
作者：
Read JF;Bosco A
人类呼吸道合胞病毒和人类鼻病毒是婴儿和儿童呼吸道感染的最常见原因，也是急性病毒性细支气管炎、喘息和哮喘恶化的主要诱因。在这里，我们将讨论应用系统生物学的强大工具来解码决定感染和随后哮喘风险的分子机制。一个重要的概念进展是认识到先天免疫系统是由蝴蝶结结构控制的，其中不同的输入信号汇聚到几个核心通路（例如 IRF7），进而产生协调效应器和调节功能的不同输出。对哮喘/喘息严重恶化的儿童进行的分子谱研究已确定了两种主要的免疫表型。 IRF7hi 表型的特点是抗病毒反应网络的强劲上调，IRF7lo 表型的特点是 TGFβ 信号传导和 2 型炎症标志物的上调。在患有严重病毒性细支气管炎的婴儿和儿童中也发现了类似的表型。值得注意的是，由实验验证支持的全基因组关联研究已经确定了增加 HRV 感染易感性（ORMDL3 和 CHDR3）和调节 TGFβ 信号传导（GSDMB、TGFBR1 和 SMAD3）的关键途径。此外，对于有发热性下呼吸道感染和持续性哮喘/喘息风险的儿童，I型和III型干扰素反应激活的功能缺陷在出生时就已经很明显，这表明哮喘的轨迹从出生时或在子宫内就开始了。最后，接触微生物及其产品会重新编程先天免疫，并防止儿童发生过敏和哮喘，因此微生物产品是哮喘一级预防的合理候选者。
Human Respiratory Syncytial Virus and Human Rhinovirus are the most frequent cause of respiratory tract infections in infants and children and are major triggers of acute viral bronchiolitis, wheezing and asthma exacerbations. Here, we will discuss the application of the powerful tools of systems biology to decode the molecular mechanisms that determine risk for infection and subsequent asthma. An important conceptual advance is the understanding that the innate immune system is governed by a Bow-tie architecture, where diverse input signals converge onto a few core pathways (e.g., IRF7), which in turn generate diverse outputs that orchestrate effector and regulatory functions. Molecular profiling studies in children with severe exacerbations of asthma/wheeze have identified two major immunological phenotypes. The IRF7hi phenotype is characterised by robust upregulation of antiviral response networks, and the IRF7lo phenotype is characterised by upregulation of markers of TGFβ signalling and type 2 inflammation. Similar phenotypes have been identified in infants and children with severe viral bronchiolitis. Notably, genome-wide association studies supported by experimental validation have identified key pathways that increase susceptibility to HRV infection (ORMDL3 and CHDR3) and modulate TGFβ signalling (GSDMB, TGFBR1, and SMAD3). Moreover, functional deficiencies in the activation of type I and III interferon responses are already evident at birth in children at risk of developing febrile lower respiratory tract infections and persistent asthma/wheeze, suggesting that the trajectory to asthma begins at birth or in utero. Finally, exposure to microbes and their products reprograms innate immunity and provides protection from the development of allergies and asthma in children, and therefore microbial products are logical candidates for the primary prevention of asthma.
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DOI：
10.1183/09031936.00092410
发表时间：
2011-05
期刊：
The European respiratory journal
影响因子：
--
作者：
Bizzintino J;Lee WM;Laing IA;Vang F;Pappas T;Zhang G;Martin AC;Khoo SK;Cox DW;Geelhoed GC;McMinn PC;Goldblatt J;Gern JE;Le Souëf PN
通讯作者：
Le Souëf PN
DOI：
10.1016/j.jaci.2011.10.038
发表时间：
2012-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Bosco A;Ehteshami S;Panyala S;Martinez FD
通讯作者：
Martinez FD
影响因子：
30.8
作者：
Demenais F;Margaritte-Jeannin P;Barnes KC;Cookson WOC;Altmüller J;Ang W;Barr RG;Beaty TH;Becker AB;Beilby J;Bisgaard H;Bjornsdottir US;Bleecker E;Bønnelykke K;Boomsma DI;Bouzigon E;Brightling CE;Brossard M;Brusselle GG;Burchard E;Burkart KM;Bush A;Chan-Yeung M;Chung KF;Couto Alves A;Curtin JA;Custovic A;Daley D;de Jongste JC;Del-Rio-Navarro BE;Donohue KM;Duijts L;Eng C;Eriksson JG;Farrall M;Fedorova Y;Feenstra B;Ferreira MA;Australian Asthma Genetics Consortium (AAGC) collaborators;Freidin MB;Gajdos Z;Gauderman J;Gehring U;Geller F;Genuneit J;Gharib SA;Gilliland F;Granell R;Graves PE;Gudbjartsson DF;Haahtela T;Heckbert SR;Heederik D;Heinrich J;Heliövaara M;Henderson J;Himes BE;Hirose H;Hirschhorn JN;Hofman A;Holt P;Hottenga J;Hudson TJ;Hui J;Imboden M;Ivanov V;Jaddoe VWV;James A;Janson C;Jarvelin MR;Jarvis D;Jones G;Jonsdottir I;Jousilahti P;Kabesch M;Kähönen M;Kantor DB;Karunas AS;Khusnutdinova E;Koppelman GH;Kozyrskyj AL;Kreiner E;Kubo M;Kumar R;Kumar A;Kuokkanen M;Lahousse L;Laitinen T;Laprise C;Lathrop M;Lau S;Lee YA;Lehtimäki T;Letort S;Levin AM;Li G;Liang L;Loehr LR;London SJ;Loth DW;Manichaikul A;Marenholz I;Martinez FJ;Matheson MC;Mathias RA;Matsumoto K;Mbarek H;McArdle WL;Melbye M;Melén E;Meyers D;Michel S;Mohamdi H;Musk AW;Myers RA;Nieuwenhuis MAE;Noguchi E;O'Connor GT;Ogorodova LM;Palmer CD;Palotie A;Park JE;Pennell CE;Pershagen G;Polonikov A;Postma DS;Probst-Hensch N;Puzyrev VP;Raby BA;Raitakari OT;Ramasamy A;Rich SS;Robertson CF;Romieu I;Salam MT;Salomaa V;Schlünssen V;Scott R;Selivanova PA;Sigsgaard T;Simpson A;Siroux V;Smith LJ;Solodilova M;Standl M;Stefansson K;Strachan DP;Stricker BH;Takahashi A;Thompson PJ;Thorleifsson G;Thorsteinsdottir U;Tiesler CMT;Torgerson DG;Tsunoda T;Uitterlinden AG;van der Valk RJP;Vaysse A;Vedantam S;von Berg A;von Mutius E;Vonk JM;Waage J;Wareham NJ;Weiss ST;White WB;Wickman M;Widén E;Willemsen G;Williams LK;Wouters IM;Yang JJ;Zhao JH;Moffatt MF;Ober C;Nicolae DL
通讯作者：
Nicolae DL
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
影响因子：
1.6
作者：
Elgizouli M;Logan C;Nieters A;Brenner H;Rothenbacher D
通讯作者：
Rothenbacher D