High secretion of interferons by human plasmacytoid dendritic cells upon recognition of Middle East respiratory syndrome coronavirus.
Identifieur interne : 001310 ( Main/Exploration ); précédent : 001309; suivant : 001311High secretion of interferons by human plasmacytoid dendritic cells upon recognition of Middle East respiratory syndrome coronavirus.
Auteurs : Vivian A. Scheuplein [Allemagne] ; Janna Seifried [Allemagne] ; Anna H. Malczyk [Allemagne] ; Lilija Miller [Allemagne] ; Lena Höcker [Allemagne] ; Júlia Vergara-Alert [Allemagne] ; Olga Dolnik [Allemagne] ; Florian Zielecki [Allemagne] ; Björn Becker [Allemagne] ; Ingo Spreitzer [Allemagne] ; Renate König [États-Unis] ; Stephan Becker [Allemagne] ; Zoe Waibler [Allemagne] ; Michael D. Mühlebach [Allemagne]Source :
- Journal of virology [ 1098-5514 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Cellules dendritiques (immunologie), Cellules dendritiques (virologie), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Dipeptidyl peptidase 4 (métabolisme), Endocytose, Endosomes (métabolisme), Endosomes (virologie), Humains, Interférons (métabolisme), Pénétration virale, Souris de lignée C57BL.
- MESH :
- immunologie : Cellules dendritiques, Coronavirus du syndrome respiratoire du Moyen-Orient.
- métabolisme : Dipeptidyl peptidase 4, Endosomes, Interférons.
- virologie : Cellules dendritiques, Endosomes.
- Animaux, Endocytose, Humains, Pénétration virale, Souris de lignée C57BL.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Dipeptidyl Peptidase 4, Interferons.
- immunology : Dendritic Cells, Middle East Respiratory Syndrome Coronavirus.
- metabolism : Endosomes.
- virology : Dendritic Cells, Endosomes.
- Animals, Endocytosis, Humans, Mice, Inbred C57BL, Virus Internalization.
Abstract
The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as the causative agent of a severe respiratory disease with a fatality rate of approximately 30%. The high virulence and mortality rate prompted us to analyze aspects of MERS-CoV pathogenesis, especially its interaction with innate immune cells such as antigen-presenting cells (APCs). Particularly, we analyzed secretion of type I and type III interferons (IFNs) by APCs, i.e., B cells, macrophages, monocyte-derived/myeloid dendritic cells (MDDCs/mDCs), and by plasmacytoid dendritic cells (pDCs) of human and murine origin after inoculation with MERS-CoV. Production of large amounts of type I and III IFNs was induced exclusively in human pDCs, which were significantly higher than IFN induction by severe acute respiratory syndrome (SARS)-CoV. Of note, IFNs were secreted in the absence of productive replication. However, receptor binding, endosomal uptake, and probably signaling via Toll-like receptor 7 (TLR7) were critical for sensing of MERS-CoV by pDCs. Furthermore, active transcription of MERS-CoV N RNA and subsequent N protein expression were evident in infected pDCs, indicating abortive infection. Taken together, our results point toward dipeptidyl peptidase 4 (DPP4)-dependent endosomal uptake and subsequent infection of human pDCs by MERS-CoV. However, the replication cycle is stopped after early gene expression. In parallel, human pDCs are potent IFN-producing cells upon MERS-CoV infection. Knowledge of such IFN responses supports our understanding of MERS-CoV pathogenesis and is critical for the choice of treatment options.
DOI: 10.1128/JVI.03607-14
PubMed: 25609809
Affiliations:
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Germany German Centre for Infection Research, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Waibler, Zoe" sort="Waibler, Zoe" uniqKey="Waibler Z" first="Zoe" last="Waibler">Zoe Waibler</name><affiliation wicri:level="1"><nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, Langen, Germany Zoe.Waibler@pei.de Michael.Muehlebach@pei.de.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>Novel Vaccination Strategies and Early Immune Responses, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, 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Scheuplein</name><affiliation wicri:level="1"><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul Ehrlich Institut, Langen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul Ehrlich Institut, Langen</wicri:regionArea><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion></affiliation></author><author><name sortKey="Seifried, Janna" sort="Seifried, Janna" uniqKey="Seifried J" first="Janna" last="Seifried">Janna Seifried</name><affiliation wicri:level="1"><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul Ehrlich Institut, Langen, Germany Host Pathogen Interactions, Paul Ehrlich Institut, Langen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul Ehrlich Institut, Langen, Germany Host Pathogen Interactions, Paul Ehrlich Institut, Langen</wicri:regionArea><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion></affiliation></author><author><name sortKey="Malczyk, Anna H" sort="Malczyk, Anna H" uniqKey="Malczyk A" first="Anna H" last="Malczyk">Anna H. Malczyk</name><affiliation wicri:level="1"><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, Langen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, Langen</wicri:regionArea><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion></affiliation></author><author><name sortKey="Miller, Lilija" sort="Miller, Lilija" uniqKey="Miller L" first="Lilija" last="Miller">Lilija Miller</name><affiliation wicri:level="1"><nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul Ehrlich Institut, Langen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Novel Vaccination Strategies and Early Immune Responses, Paul Ehrlich Institut, Langen</wicri:regionArea><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion></affiliation></author><author><name sortKey="Hocker, Lena" sort="Hocker, Lena" uniqKey="Hocker L" first="Lena" last="Höcker">Lena Höcker</name><affiliation wicri:level="1"><nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul Ehrlich Institut, Langen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Novel Vaccination Strategies and Early Immune Responses, Paul Ehrlich Institut, Langen</wicri:regionArea><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion></affiliation></author><author><name sortKey="Vergara Alert, Julia" sort="Vergara Alert, Julia" uniqKey="Vergara Alert J" first="Júlia" last="Vergara-Alert">Júlia Vergara-Alert</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Centre for Infection Research, Marburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Centre for Infection Research, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Dolnik, Olga" sort="Dolnik, Olga" uniqKey="Dolnik O" first="Olga" last="Dolnik">Olga Dolnik</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Zielecki, Florian" sort="Zielecki, Florian" uniqKey="Zielecki F" first="Florian" last="Zielecki">Florian Zielecki</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Becker, Bjorn" sort="Becker, Bjorn" uniqKey="Becker B" first="Björn" last="Becker">Björn Becker</name><affiliation wicri:level="1"><nlm:affiliation>Bacterial Safety, Paul Ehrlich Institut, Langen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bacterial Safety, Paul Ehrlich Institut, Langen</wicri:regionArea><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion></affiliation></author><author><name sortKey="Spreitzer, Ingo" sort="Spreitzer, Ingo" uniqKey="Spreitzer I" first="Ingo" last="Spreitzer">Ingo Spreitzer</name><affiliation wicri:level="1"><nlm:affiliation>Bacterial Safety, Paul Ehrlich Institut, Langen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bacterial Safety, Paul Ehrlich Institut, Langen</wicri:regionArea><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion></affiliation></author><author><name sortKey="Konig, Renate" sort="Konig, Renate" uniqKey="Konig R" first="Renate" last="König">Renate König</name><affiliation wicri:level="1"><nlm:affiliation>Host Pathogen Interactions, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, Langen, Germany Sanford-Burnham Medical Research Institute, Infectious and Inflammatory Disease Center, La Jolla, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Host Pathogen Interactions, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, Langen, Germany Sanford-Burnham Medical Research Institute, Infectious and Inflammatory Disease Center, La Jolla</wicri:regionArea><wicri:noRegion>La Jolla</wicri:noRegion></affiliation></author><author><name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Centre for Infection Research, Marburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institut für Virologie, Philipps Universität Marburg, Marburg, Germany German Centre for Infection Research, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Waibler, Zoe" sort="Waibler, Zoe" uniqKey="Waibler Z" first="Zoe" last="Waibler">Zoe Waibler</name><affiliation wicri:level="1"><nlm:affiliation>Novel Vaccination Strategies and Early Immune Responses, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, Langen, Germany Zoe.Waibler@pei.de Michael.Muehlebach@pei.de.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>Novel Vaccination Strategies and Early Immune Responses, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, Langen</wicri:regionArea><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion></affiliation></author><author><name sortKey="Muhlebach, Michael D" sort="Muhlebach, Michael D" uniqKey="Muhlebach M" first="Michael D" last="Mühlebach">Michael D. Mühlebach</name><affiliation wicri:level="1"><nlm:affiliation>Oncolytic Measles Viruses and Vaccine Vectors, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, Langen, Germany Zoe.Waibler@pei.de Michael.Muehlebach@pei.de.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>Oncolytic Measles Viruses and Vaccine Vectors, Paul Ehrlich Institut, Langen, Germany German Center for Infection Research, Langen</wicri:regionArea><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion><wicri:noRegion>Langen</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Dendritic Cells (immunology)</term><term>Dendritic Cells (virology)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Endocytosis</term><term>Endosomes (metabolism)</term><term>Endosomes (virology)</term><term>Humans</term><term>Interferons (metabolism)</term><term>Mice, Inbred C57BL</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules dendritiques (immunologie)</term><term>Cellules dendritiques (virologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Dipeptidyl peptidase 4 (métabolisme)</term><term>Endocytose</term><term>Endosomes (métabolisme)</term><term>Endosomes (virologie)</term><term>Humains</term><term>Interférons (métabolisme)</term><term>Pénétration virale</term><term>Souris de lignée C57BL</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Interferons</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules dendritiques</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Dendritic Cells</term><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endosomes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Dipeptidyl peptidase 4</term><term>Endosomes</term><term>Interférons</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Cellules dendritiques</term><term>Endosomes</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Dendritic Cells</term><term>Endosomes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Endocytosis</term><term>Humans</term><term>Mice, Inbred C57BL</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Endocytose</term><term>Humains</term><term>Pénétration virale</term><term>Souris de lignée C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as the causative agent of a severe respiratory disease with a fatality rate of approximately 30%. The high virulence and mortality rate prompted us to analyze aspects of MERS-CoV pathogenesis, especially its interaction with innate immune cells such as antigen-presenting cells (APCs). Particularly, we analyzed secretion of type I and type III interferons (IFNs) by APCs, i.e., B cells, macrophages, monocyte-derived/myeloid dendritic cells (MDDCs/mDCs), and by plasmacytoid dendritic cells (pDCs) of human and murine origin after inoculation with MERS-CoV. Production of large amounts of type I and III IFNs was induced exclusively in human pDCs, which were significantly higher than IFN induction by severe acute respiratory syndrome (SARS)-CoV. Of note, IFNs were secreted in the absence of productive replication. However, receptor binding, endosomal uptake, and probably signaling via Toll-like receptor 7 (TLR7) were critical for sensing of MERS-CoV by pDCs. Furthermore, active transcription of MERS-CoV N RNA and subsequent N protein expression were evident in infected pDCs, indicating abortive infection. Taken together, our results point toward dipeptidyl peptidase 4 (DPP4)-dependent endosomal uptake and subsequent infection of human pDCs by MERS-CoV. However, the replication cycle is stopped after early gene expression. In parallel, human pDCs are potent IFN-producing cells upon MERS-CoV infection. Knowledge of such IFN responses supports our understanding of MERS-CoV pathogenesis and is critical for the choice of treatment options.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>États-Unis</li></country><region><li>District de Giessen</li><li>Hesse (Land)</li></region><settlement><li>Marbourg</li></settlement></list><tree><country name="Allemagne"><noRegion><name sortKey="Scheuplein, Vivian A" sort="Scheuplein, Vivian A" uniqKey="Scheuplein V" first="Vivian A" last="Scheuplein">Vivian A. Scheuplein</name></noRegion><name sortKey="Becker, Bjorn" sort="Becker, Bjorn" uniqKey="Becker B" first="Björn" last="Becker">Björn Becker</name><name sortKey="Becker, Stephan" sort="Becker, Stephan" uniqKey="Becker S" first="Stephan" last="Becker">Stephan Becker</name><name sortKey="Dolnik, Olga" sort="Dolnik, Olga" uniqKey="Dolnik O" first="Olga" last="Dolnik">Olga Dolnik</name><name sortKey="Hocker, Lena" sort="Hocker, Lena" uniqKey="Hocker L" first="Lena" last="Höcker">Lena Höcker</name><name sortKey="Malczyk, Anna H" sort="Malczyk, Anna H" uniqKey="Malczyk A" first="Anna H" last="Malczyk">Anna H. Malczyk</name><name sortKey="Miller, Lilija" sort="Miller, Lilija" uniqKey="Miller L" first="Lilija" last="Miller">Lilija Miller</name><name sortKey="Muhlebach, Michael D" sort="Muhlebach, Michael D" uniqKey="Muhlebach M" first="Michael D" last="Mühlebach">Michael D. Mühlebach</name><name sortKey="Seifried, Janna" sort="Seifried, Janna" uniqKey="Seifried J" first="Janna" last="Seifried">Janna Seifried</name><name sortKey="Spreitzer, Ingo" sort="Spreitzer, Ingo" uniqKey="Spreitzer I" first="Ingo" last="Spreitzer">Ingo Spreitzer</name><name sortKey="Vergara Alert, Julia" sort="Vergara Alert, Julia" uniqKey="Vergara Alert J" first="Júlia" last="Vergara-Alert">Júlia Vergara-Alert</name><name sortKey="Waibler, Zoe" sort="Waibler, Zoe" uniqKey="Waibler Z" first="Zoe" last="Waibler">Zoe Waibler</name><name sortKey="Zielecki, Florian" sort="Zielecki, Florian" uniqKey="Zielecki F" first="Florian" last="Zielecki">Florian Zielecki</name></country><country name="États-Unis"><noRegion><name sortKey="Konig, Renate" sort="Konig, Renate" uniqKey="Konig R" first="Renate" last="König">Renate König</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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