Serveur d'exploration MERS

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Activation of C-Type Lectin Receptor and (RIG)-I-Like Receptors Contributes to Proinflammatory Response in Middle East Respiratory Syndrome Coronavirus-Infected Macrophages

Identifieur interne : 000714 ( Main/Exploration ); précédent : 000713; suivant : 000715

Activation of C-Type Lectin Receptor and (RIG)-I-Like Receptors Contributes to Proinflammatory Response in Middle East Respiratory Syndrome Coronavirus-Infected Macrophages

Auteurs : Xiaoyu Zhao [Hong Kong] ; Hin Chu [Hong Kong] ; Bosco Ho-Yin Wong [Hong Kong] ; Man Chun Chiu [Hong Kong] ; Dong Wang [Hong Kong] ; Cun Li [Hong Kong] ; Xiaojuan Liu [Hong Kong] ; Dong Yang [Hong Kong] ; Vincent Kwok-Man Poon [Hong Kong] ; Jianpiao Cai [Hong Kong] ; Jasper Fuk-Woo Chan [Hong Kong] ; Kelvin Kai-Wang To [Hong Kong] ; Jie Zhou [Hong Kong] ; Kwok-Yung Yuen [Hong Kong]

Source :

RBID : PMC:7107474

Abstract

AbstractBackground

Human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) poses an ongoing threat to public health worldwide. The studies of MERS patients with severe disease and experimentally infected animals showed that robust viral replication and intensive proinflammatory response in lung tissues contribute to high pathogenicity of MERS-CoV. We sought to identify pattern recognition receptor (PRR) signaling pathway(s) that mediates the inflammatory cascade in human macrophages upon MERS-CoV infection.

Methods

The potential signaling pathways were manipulated individually by pharmacological inhibition, small interfering ribonucleic acid (siRNA) depletion, and antibody blocking. The MERS-CoV-induced proinflammatory response was evaluated by measuring the expression levels of key cytokines and/or chemokines. Reverse transcription-quantitative polymerase chain reaction assay, flow cytometry analysis, and Western blotting were applied to evaluate the activation of related PRRs and engagement of adaptors.

Results

MERS-CoV replication significantly upregulated C-type lectin receptor (CLR) macrophage-inducible Ca2+-dependent lectin receptor (Mincle). The role of Mincle for MERS-CoV-triggered cytokine/chemokine induction was established based on the results of antibody blockage, siRNA depletion of Mincle and its adaptor spleen tyrosine kinase (Syk), and Syk pharmacological inhibition. The cytokine and/or chemokine induction was significantly attenuated by siRNA depletion of retinoic acid-inducible-I-like receptors (RLR) or adaptor, indicating that RLR signaling also contributed to MERS-CoV-induced proinflammatory response.

Conclusions

The CLR and RLR pathways are activated and contribute to the proinflammatory response in MERS-CoV-infected macrophages.


Url:
DOI: 10.1093/infdis/jiz483
PubMed: 31562757
PubMed Central: 7107474


Affiliations:


Links toward previous steps (curation, corpus...)


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<name sortKey="Poon, Vincent Kwok Man" sort="Poon, Vincent Kwok Man" uniqKey="Poon V" first="Vincent Kwok-Man" last="Poon">Vincent Kwok-Man Poon</name>
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<name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<nlm:aff id="AF0003">
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, Pokfulam,
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<institution>State Key Laboratory of Emerging Infectious Diseases</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="AF0002">
<institution>Department of Microbiology</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="AF0003">
<institution>Carol Yu Centre for Infection</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="AF0004">
<institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
<affiliation wicri:level="1">
<nlm:aff id="AF0001">
<institution>State Key Laboratory of Emerging Infectious Diseases</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="AF0002">
<institution>Department of Microbiology</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation wicri:level="1">
<nlm:aff id="AF0001">
<institution>State Key Laboratory of Emerging Infectious Diseases</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="AF0002">
<institution>Department of Microbiology</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="AF0003">
<institution>Carol Yu Centre for Infection</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="AF0004">
<institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong</institution>
, Pokfulam,
<country country="HK">Hong Kong</country>
</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The Journal of Infectious Diseases</title>
<idno type="ISSN">0022-1899</idno>
<idno type="eISSN">1537-6613</idno>
<imprint>
<date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<title>Abstract</title>
<sec id="s0100">
<title>Background</title>
<p>Human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) poses an ongoing threat to public health worldwide. The studies of MERS patients with severe disease and experimentally infected animals showed that robust viral replication and intensive proinflammatory response in lung tissues contribute to high pathogenicity of MERS-CoV. We sought to identify pattern recognition receptor (PRR) signaling pathway(s) that mediates the inflammatory cascade in human macrophages upon MERS-CoV infection.</p>
</sec>
<sec id="s0101">
<title>Methods</title>
<p>The potential signaling pathways were manipulated individually by pharmacological inhibition, small interfering ribonucleic acid (siRNA) depletion, and antibody blocking. The MERS-CoV-induced proinflammatory response was evaluated by measuring the expression levels of key cytokines and/or chemokines. Reverse transcription-quantitative polymerase chain reaction assay, flow cytometry analysis, and Western blotting were applied to evaluate the activation of related PRRs and engagement of adaptors.</p>
</sec>
<sec id="s0102">
<title>Results</title>
<p>MERS-CoV replication significantly upregulated C-type lectin receptor (CLR) macrophage-inducible Ca
<sup>2+</sup>
-dependent lectin receptor (Mincle). The role of Mincle for MERS-CoV-triggered cytokine/chemokine induction was established based on the results of antibody blockage, siRNA depletion of Mincle and its adaptor spleen tyrosine kinase (Syk), and Syk pharmacological inhibition. The cytokine and/or chemokine induction was significantly attenuated by siRNA depletion of retinoic acid-inducible-I-like receptors (RLR) or adaptor, indicating that RLR signaling also contributed to MERS-CoV-induced proinflammatory response.</p>
</sec>
<sec id="s0103">
<title>Conclusions</title>
<p>The CLR and RLR pathways are activated and contribute to the proinflammatory response in MERS-CoV-infected macrophages.</p>
</sec>
</div>
</front>
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<biblStruct>
<analytic>
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<name sortKey="Ferwerda, G" uniqKey="Ferwerda G">G Ferwerda</name>
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<name sortKey="Kullberg, Bj" uniqKey="Kullberg B">BJ Kullberg</name>
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<name sortKey="De Jong, Dj" uniqKey="De Jong D">DJ de Jong</name>
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<li>Hong Kong</li>
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<name sortKey="Zhao, Xiaoyu" sort="Zhao, Xiaoyu" uniqKey="Zhao X" first="Xiaoyu" last="Zhao">Xiaoyu Zhao</name>
</noRegion>
<name sortKey="Cai, Jianpiao" sort="Cai, Jianpiao" uniqKey="Cai J" first="Jianpiao" last="Cai">Jianpiao Cai</name>
<name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
<name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
<name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
<name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
<name sortKey="Chiu, Man Chun" sort="Chiu, Man Chun" uniqKey="Chiu M" first="Man Chun" last="Chiu">Man Chun Chiu</name>
<name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name>
<name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name>
<name sortKey="Li, Cun" sort="Li, Cun" uniqKey="Li C" first="Cun" last="Li">Cun Li</name>
<name sortKey="Liu, Xiaojuan" sort="Liu, Xiaojuan" uniqKey="Liu X" first="Xiaojuan" last="Liu">Xiaojuan Liu</name>
<name sortKey="Poon, Vincent Kwok Man" sort="Poon, Vincent Kwok Man" uniqKey="Poon V" first="Vincent Kwok-Man" last="Poon">Vincent Kwok-Man Poon</name>
<name sortKey="To, Kelvin Kai Wang" sort="To, Kelvin Kai Wang" uniqKey="To K" first="Kelvin Kai-Wang" last="To">Kelvin Kai-Wang To</name>
<name sortKey="To, Kelvin Kai Wang" sort="To, Kelvin Kai Wang" uniqKey="To K" first="Kelvin Kai-Wang" last="To">Kelvin Kai-Wang To</name>
<name sortKey="To, Kelvin Kai Wang" sort="To, Kelvin Kai Wang" uniqKey="To K" first="Kelvin Kai-Wang" last="To">Kelvin Kai-Wang To</name>
<name sortKey="To, Kelvin Kai Wang" sort="To, Kelvin Kai Wang" uniqKey="To K" first="Kelvin Kai-Wang" last="To">Kelvin Kai-Wang To</name>
<name sortKey="Wang, Dong" sort="Wang, Dong" uniqKey="Wang D" first="Dong" last="Wang">Dong Wang</name>
<name sortKey="Wong, Bosco Ho Yin" sort="Wong, Bosco Ho Yin" uniqKey="Wong B" first="Bosco Ho-Yin" last="Wong">Bosco Ho-Yin Wong</name>
<name sortKey="Yang, Dong" sort="Yang, Dong" uniqKey="Yang D" first="Dong" last="Yang">Dong Yang</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Zhao, Xiaoyu" sort="Zhao, Xiaoyu" uniqKey="Zhao X" first="Xiaoyu" last="Zhao">Xiaoyu Zhao</name>
<name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
<name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
</country>
</tree>
</affiliations>
</record>

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