Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza.
Identifieur interne : 000966 ( Main/Exploration ); précédent : 000965; suivant : 000967Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza.
Auteurs : Jake Dunning [Royaume-Uni] ; Simon Blankley [Royaume-Uni] ; Long T. Hoang [Royaume-Uni] ; Mike Cox [Royaume-Uni] ; Christine M. Graham [Royaume-Uni] ; Philip L. James [Royaume-Uni] ; Chloe I. Bloom [Royaume-Uni] ; Damien Chaussabel [Qatar] ; Jacques Banchereau [États-Unis] ; Stephen J. Brett [Royaume-Uni] ; Miriam F. Moffatt [Royaume-Uni] ; Anne O'Garra [Royaume-Uni] ; Peter J M. Openshaw [Royaume-Uni]Source :
- Nature immunology [ 1529-2916 ] ; 2018.
Descripteurs français
- KwdFr :
- ARN messager (sang), Adolescent, Adulte, Adulte d'âge moyen, Femelle, Granulocytes neutrophiles (immunologie), Grippe humaine (génétique), Grippe humaine (immunologie), Grippe humaine (sang), Humains, Interférons (immunologie), Interférons (sang), Jeune adulte, Marqueurs biologiques (sang), Mâle, Sujet âgé, Transcriptome, Évolution de la maladie.
- MESH :
- génétique : Grippe humaine.
- immunologie : Granulocytes neutrophiles, Grippe humaine, Interférons.
- sang : ARN messager, Grippe humaine, Interférons, Marqueurs biologiques.
- Adolescent, Adulte, Adulte d'âge moyen, Femelle, Humains, Jeune adulte, Mâle, Sujet âgé, Transcriptome, Évolution de la maladie.
English descriptors
- KwdEn :
- Adolescent, Adult, Aged, Biomarkers (blood), Disease Progression, Female, Humans, Influenza, Human (blood), Influenza, Human (genetics), Influenza, Human (immunology), Interferons (blood), Interferons (immunology), Male, Middle Aged, Neutrophils (immunology), RNA, Messenger (blood), Transcriptome, Young Adult.
- MESH :
- chemical , blood : Biomarkers, Interferons, RNA, Messenger.
- blood : Influenza, Human.
- genetics : Influenza, Human.
- immunology : Influenza, Human, Interferons, Neutrophils.
- Adolescent, Adult, Aged, Disease Progression, Female, Humans, Male, Middle Aged, Transcriptome, Young Adult.
Abstract
Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death ('bacterial') pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this 'bacterial' signature but was able to enhance its development while attenuating the early 'viral' signature. Our findings emphasize the importance of timing and severity in the interpretation of host responses to acute viral infection and identify specific patterns of immune-system activation that might enable the development of novel diagnostic and therapeutic tools for severe influenza.
DOI: 10.1038/s41590-018-0111-5
PubMed: 29777224
Affiliations:
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Le document en format XML
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Hoang</name><affiliation wicri:level="3"><nlm:affiliation>Respiratory Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Respiratory Infection Section, National Heart and Lung Institute, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Cox, Mike" sort="Cox, Mike" uniqKey="Cox M" first="Mike" last="Cox">Mike Cox</name><affiliation wicri:level="3"><nlm:affiliation>Genomic Medicine, National Heart and Lung Institute, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genomic Medicine, National Heart and Lung Institute, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Graham, Christine M" sort="Graham, Christine M" uniqKey="Graham C" first="Christine M" last="Graham">Christine M. Graham</name><affiliation wicri:level="3"><nlm:affiliation>Laboratory of Immunoregulation & Infection, The Francis Crick Institute, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Immunoregulation & Infection, The Francis Crick Institute, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="James, Philip L" sort="James, Philip L" uniqKey="James P" first="Philip L" last="James">Philip L. James</name><affiliation wicri:level="3"><nlm:affiliation>Genomic Medicine, National Heart and Lung Institute, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genomic Medicine, National Heart and Lung Institute, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Bloom, Chloe I" sort="Bloom, Chloe I" uniqKey="Bloom C" first="Chloe I" last="Bloom">Chloe I. Bloom</name><affiliation wicri:level="3"><nlm:affiliation>Laboratory of Immunoregulation & Infection, The Francis Crick Institute, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Immunoregulation & Infection, The Francis Crick Institute, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Chaussabel, Damien" sort="Chaussabel, Damien" uniqKey="Chaussabel D" first="Damien" last="Chaussabel">Damien Chaussabel</name><affiliation wicri:level="1"><nlm:affiliation>Sidra Medical and Research Centre, Doha, Qatar.</nlm:affiliation><country xml:lang="fr">Qatar</country><wicri:regionArea>Sidra Medical and Research Centre, Doha</wicri:regionArea><wicri:noRegion>Doha</wicri:noRegion></affiliation></author><author><name sortKey="Banchereau, Jacques" sort="Banchereau, Jacques" uniqKey="Banchereau J" first="Jacques" last="Banchereau">Jacques Banchereau</name><affiliation wicri:level="1"><nlm:affiliation>The Jackson Laboratory for Genomic Medicine, Farmington, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Jackson Laboratory for Genomic Medicine, Farmington</wicri:regionArea><wicri:noRegion>Farmington</wicri:noRegion></affiliation></author><author><name sortKey="Brett, Stephen J" sort="Brett, Stephen J" uniqKey="Brett S" first="Stephen J" last="Brett">Stephen J. Brett</name><affiliation wicri:level="3"><nlm:affiliation>Surgery and Cancer, National Heart and Lung Institute, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Surgery and Cancer, National Heart and Lung Institute, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Moffatt, Miriam F" sort="Moffatt, Miriam F" uniqKey="Moffatt M" first="Miriam F" last="Moffatt">Miriam F. Moffatt</name><affiliation wicri:level="3"><nlm:affiliation>Genomic Medicine, National Heart and Lung Institute, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genomic Medicine, National Heart and Lung Institute, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="O Garra, Anne" sort="O Garra, Anne" uniqKey="O Garra A" first="Anne" last="O'Garra">Anne O'Garra</name><affiliation wicri:level="3"><nlm:affiliation>Laboratory of Immunoregulation & Infection, The Francis Crick Institute, London, UK. anne.ogarra@crick.ac.uk.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Immunoregulation & Infection, The Francis Crick Institute, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Openshaw, Peter J M" sort="Openshaw, Peter J M" uniqKey="Openshaw P" first="Peter J M" last="Openshaw">Peter J M. Openshaw</name><affiliation wicri:level="3"><nlm:affiliation>Respiratory Infection Section, National Heart and Lung Institute, Imperial College London, London, UK. p.openshaw@imperial.ac.uk.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Respiratory Infection Section, National Heart and Lung Institute, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">Nature immunology</title><idno type="eISSN">1529-2916</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Biomarkers (blood)</term><term>Disease Progression</term><term>Female</term><term>Humans</term><term>Influenza, Human (blood)</term><term>Influenza, Human (genetics)</term><term>Influenza, Human (immunology)</term><term>Interferons (blood)</term><term>Interferons (immunology)</term><term>Male</term><term>Middle Aged</term><term>Neutrophils (immunology)</term><term>RNA, Messenger (blood)</term><term>Transcriptome</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (sang)</term><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Femelle</term><term>Granulocytes neutrophiles (immunologie)</term><term>Grippe humaine (génétique)</term><term>Grippe humaine (immunologie)</term><term>Grippe humaine (sang)</term><term>Humains</term><term>Interférons (immunologie)</term><term>Interférons (sang)</term><term>Jeune adulte</term><term>Marqueurs biologiques (sang)</term><term>Mâle</term><term>Sujet âgé</term><term>Transcriptome</term><term>Évolution de la maladie</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Biomarkers</term><term>Interferons</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Grippe humaine</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Granulocytes neutrophiles</term><term>Grippe humaine</term><term>Interférons</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza, Human</term><term>Interferons</term><term>Neutrophils</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>ARN messager</term><term>Grippe humaine</term><term>Interférons</term><term>Marqueurs biologiques</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Disease Progression</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Transcriptome</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Mâle</term><term>Sujet âgé</term><term>Transcriptome</term><term>Évolution de la maladie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death ('bacterial') pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this 'bacterial' signature but was able to enhance its development while attenuating the early 'viral' signature. Our findings emphasize the importance of timing and severity in the interpretation of host responses to acute viral infection and identify specific patterns of immune-system activation that might enable the development of novel diagnostic and therapeutic tools for severe influenza.</div></front></TEI><affiliations><list><country><li>Qatar</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Dunning, Jake" sort="Dunning, Jake" uniqKey="Dunning J" first="Jake" last="Dunning">Jake Dunning</name></region><name sortKey="Blankley, Simon" sort="Blankley, Simon" uniqKey="Blankley S" first="Simon" last="Blankley">Simon Blankley</name><name sortKey="Bloom, Chloe I" sort="Bloom, Chloe I" uniqKey="Bloom C" first="Chloe I" last="Bloom">Chloe I. Bloom</name><name sortKey="Brett, Stephen J" sort="Brett, Stephen J" uniqKey="Brett S" first="Stephen J" last="Brett">Stephen J. Brett</name><name sortKey="Cox, Mike" sort="Cox, Mike" uniqKey="Cox M" first="Mike" last="Cox">Mike Cox</name><name sortKey="Graham, Christine M" sort="Graham, Christine M" uniqKey="Graham C" first="Christine M" last="Graham">Christine M. Graham</name><name sortKey="Hoang, Long T" sort="Hoang, Long T" uniqKey="Hoang L" first="Long T" last="Hoang">Long T. Hoang</name><name sortKey="James, Philip L" sort="James, Philip L" uniqKey="James P" first="Philip L" last="James">Philip L. James</name><name sortKey="Moffatt, Miriam F" sort="Moffatt, Miriam F" uniqKey="Moffatt M" first="Miriam F" last="Moffatt">Miriam F. Moffatt</name><name sortKey="O Garra, Anne" sort="O Garra, Anne" uniqKey="O Garra A" first="Anne" last="O'Garra">Anne O'Garra</name><name sortKey="Openshaw, Peter J M" sort="Openshaw, Peter J M" uniqKey="Openshaw P" first="Peter J M" last="Openshaw">Peter J M. Openshaw</name></country><country name="Qatar"><noRegion><name sortKey="Chaussabel, Damien" sort="Chaussabel, Damien" uniqKey="Chaussabel D" first="Damien" last="Chaussabel">Damien Chaussabel</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Banchereau, Jacques" sort="Banchereau, Jacques" uniqKey="Banchereau J" first="Jacques" last="Banchereau">Jacques Banchereau</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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