Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV
Identifieur interne : 000652 ( Main/Exploration ); précédent : 000651; suivant : 000653Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV
Auteurs : Yuting Jiang ; Junfeng Li ; Yue Teng ; Hong Sun ; Guang Tian ; Lei He ; Pei Li ; Yuehong Chen ; Yan Guo ; Jiangfan Li ; Guangyu Zhao ; Yusen Zhou [République populaire de Chine] ; Shihui SunSource :
- Viruses [ 1999-4915 ] ; 2019.
Descripteurs français
- KwdFr :
- Activation du complément, Animaux, Caspase-1 (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient, Dipeptidyl peptidase 4 (génétique), Femelle, Humains, Infections à coronavirus (anatomopathologie), Infections à coronavirus (immunologie), Interleukine-1 bêta (sang), Macrophages (immunologie), Macrophages (virologie), Modèles animaux de maladie humaine, Pyroptose, Rate (immunologie), Récepteur à l'anaphylatoxine C5a (antagonistes et inhibiteurs), Récepteur à l'anaphylatoxine C5a (immunologie), Souris, Souris transgéniques.
- MESH :
- anatomopathologie : Infections à coronavirus.
- antagonistes et inhibiteurs : Récepteur à l'anaphylatoxine C5a.
- génétique : Caspase-1, Dipeptidyl peptidase 4.
- immunologie : Infections à coronavirus, Macrophages, Rate, Récepteur à l'anaphylatoxine C5a.
- sang : Interleukine-1 bêta.
- virologie : Macrophages.
- Activation du complément, Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient, Femelle, Humains, Modèles animaux de maladie humaine, Pyroptose, Souris, Souris transgéniques.
English descriptors
- KwdEn :
- Animals, Caspase 1 (genetics), Complement Activation, Coronavirus Infections (immunology), Coronavirus Infections (pathology), Dipeptidyl Peptidase 4 (genetics), Disease Models, Animal, Female, Humans, Interleukin-1beta (blood), Macrophages (immunology), Macrophages (virology), Mice, Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus, Pyroptosis, Receptor, Anaphylatoxin C5a (antagonists & inhibitors), Receptor, Anaphylatoxin C5a (immunology), Spleen (immunology), THP-1 Cells.
- MESH :
- chemical , antagonists & inhibitors : Receptor, Anaphylatoxin C5a.
- chemical , blood : Interleukin-1beta.
- chemical , genetics : Caspase 1, Dipeptidyl Peptidase 4.
- immunology : Coronavirus Infections, Macrophages, Receptor, Anaphylatoxin C5a, Spleen.
- pathology : Coronavirus Infections.
- virology : Macrophages.
- Animals, Complement Activation, Disease Models, Animal, Female, Humans, Mice, Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus, Pyroptosis, THP-1 Cells.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1β levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1β fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.
Url:
DOI: 10.3390/v11010039
PubMed: 30634407
PubMed Central: 6356766
Affiliations:
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Le document en format XML
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China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="He, Lei" sort="He, Lei" uniqKey="He L" first="Lei" last="He">Lei He</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> 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Chen</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Guo, Yan" sort="Guo, Yan" uniqKey="Guo Y" first="Yan" last="Guo">Yan Guo</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> 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(Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-viruses-11-00039">Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052</wicri:regionArea><wicri:noRegion>Zhengzhou 450052</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30634407</idno><idno type="pmc">6356766</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356766</idno><idno 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(Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Li, Junfeng" sort="Li, Junfeng" uniqKey="Li J" first="Junfeng" last="Li">Junfeng Li</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Teng, Yue" sort="Teng, Yue" uniqKey="Teng Y" first="Yue" last="Teng">Yue Teng</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Sun, Hong" sort="Sun, Hong" uniqKey="Sun H" first="Hong" last="Sun">Hong Sun</name><affiliation><nlm:aff id="af2-viruses-11-00039">Department of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, China;<email>xun1@hotmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Tian, Guang" sort="Tian, Guang" uniqKey="Tian G" first="Guang" last="Tian">Guang Tian</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="He, Lei" sort="He, Lei" uniqKey="He L" first="Lei" last="He">Lei He</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Li, Pei" sort="Li, Pei" uniqKey="Li P" first="Pei" last="Li">Pei Li</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Yuehong" sort="Chen, Yuehong" uniqKey="Chen Y" first="Yuehong" last="Chen">Yuehong Chen</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Guo, Yan" sort="Guo, Yan" uniqKey="Guo Y" first="Yan" last="Guo">Yan Guo</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Li, Jiangfan" sort="Li, Jiangfan" uniqKey="Li J" first="Jiangfan" last="Li">Jiangfan Li</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author><author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-viruses-11-00039">Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052</wicri:regionArea><wicri:noRegion>Zhengzhou 450052</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name><affiliation><nlm:aff id="af1-viruses-11-00039">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;<email>captain99@126.com</email> (Y.J.);<email>lijunfeng2113@126.com</email> (J.L.);<email>yueteng@me.com</email> (Y.T.);<email>tglnx05@tom.com</email> (G.T.);<email>helei_happy@126.com</email> (L.H.);<email>lwhisperer@163.com</email> (P.L.);<email>chenyuehong.happy@163.com</email> (Y.C.);<email>muhan0425@126.com</email> (Y.G.);<email>anatee@163.com</email> (J.L.)<email>guangyu0525@163.com</email> (G.Z.)</nlm:aff></affiliation></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Caspase 1 (genetics)</term><term>Complement Activation</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (pathology)</term><term>Dipeptidyl Peptidase 4 (genetics)</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Interleukin-1beta (blood)</term><term>Macrophages (immunology)</term><term>Macrophages (virology)</term><term>Mice</term><term>Mice, Transgenic</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>Pyroptosis</term><term>Receptor, Anaphylatoxin C5a (antagonists & inhibitors)</term><term>Receptor, Anaphylatoxin C5a (immunology)</term><term>Spleen (immunology)</term><term>THP-1 Cells</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation du complément</term><term>Animaux</term><term>Caspase-1 (génétique)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Dipeptidyl peptidase 4 (génétique)</term><term>Femelle</term><term>Humains</term><term>Infections à coronavirus (anatomopathologie)</term><term>Infections à coronavirus (immunologie)</term><term>Interleukine-1 bêta (sang)</term><term>Macrophages (immunologie)</term><term>Macrophages (virologie)</term><term>Modèles animaux de maladie humaine</term><term>Pyroptose</term><term>Rate (immunologie)</term><term>Récepteur à l'anaphylatoxine C5a (antagonistes et inhibiteurs)</term><term>Récepteur à l'anaphylatoxine C5a (immunologie)</term><term>Souris</term><term>Souris transgéniques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Receptor, Anaphylatoxin C5a</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Interleukin-1beta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Caspase 1</term><term>Dipeptidyl Peptidase 4</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Récepteur à l'anaphylatoxine C5a</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Caspase-1</term><term>Dipeptidyl peptidase 4</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Macrophages</term><term>Rate</term><term>Récepteur à l'anaphylatoxine C5a</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term><term>Macrophages</term><term>Receptor, Anaphylatoxin C5a</term><term>Spleen</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Interleukine-1 bêta</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Macrophages</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Complement Activation</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>Pyroptosis</term><term>THP-1 Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation du complément</term><term>Animaux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Femelle</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Pyroptose</term><term>Souris</term><term>Souris transgéniques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1β levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1β fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. 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