Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection

The influenza A virus (IAV) causes a respiratory tract infection with approximately 10% of the population infected by the virus each year. Severe IAV infection is characterized by excessive inflammation and tissue pathology in the lungs. Platelet and neutrophil recruitment to the lung are involved i...

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Autores principales:	Seok-Joo Kim, Agostina Carestia, Braedon McDonald, Amanda Z. Zucoloto, Heidi Grosjean, Rachelle P. Davis, Madison Turk, Victor Naumenko, Silvio Antoniak, Nigel Mackman, Mohamed Sarjoon Abdul-Cader, Mohamed Faizal Abdul-Careem, Morley D. Hollenberg, Craig N. Jenne
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	influenza A virus platelets PAR4 thrombin neutrophils NETs Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/dca945b9c1d943fb8ab37151fffb8218
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spelling	oai:doaj.org-article:dca945b9c1d943fb8ab37151fffb82182021-11-11T09:17:54ZPlatelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection1664-322410.3389/fimmu.2021.772859https://doaj.org/article/dca945b9c1d943fb8ab37151fffb82182021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.772859/fullhttps://doaj.org/toc/1664-3224The influenza A virus (IAV) causes a respiratory tract infection with approximately 10% of the population infected by the virus each year. Severe IAV infection is characterized by excessive inflammation and tissue pathology in the lungs. Platelet and neutrophil recruitment to the lung are involved in the pathogenesis of IAV, but the specific mechanisms involved have not been clarified. Using confocal intravital microscopy in a mouse model of IAV infection, we observed profound neutrophil recruitment, platelet aggregation, neutrophil extracellular trap (NET) production and thrombin activation within the lung microvasculature in vivo. Importantly, deficiency or antagonism of the protease-activated receptor 4 (PAR4) reduced platelet aggregation, NET production, and neutrophil recruitment. Critically, inhibition of thrombin or PAR4 protected mice from virus-induced lung tissue damage and edema. Together, these data imply thrombin-stimulated platelets play a critical role in the activation/recruitment of neutrophils, NET release and directly contribute to IAV pathogenesis in the lung.Seok-Joo KimAgostina CarestiaBraedon McDonaldAmanda Z. ZucolotoHeidi GrosjeanRachelle P. DavisMadison TurkVictor NaumenkoSilvio AntoniakNigel MackmanMohamed Sarjoon Abdul-CaderMohamed Faizal Abdul-CareemMorley D. HollenbergCraig N. JenneFrontiers Media S.A.articleinfluenza A virusplateletsPAR4thrombinneutrophilsNETsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	influenza A virus platelets PAR4 thrombin neutrophils NETs Immunologic diseases. Allergy RC581-607
spellingShingle	influenza A virus platelets PAR4 thrombin neutrophils NETs Immunologic diseases. Allergy RC581-607 Seok-Joo Kim Agostina Carestia Braedon McDonald Amanda Z. Zucoloto Heidi Grosjean Rachelle P. Davis Madison Turk Victor Naumenko Silvio Antoniak Nigel Mackman Mohamed Sarjoon Abdul-Cader Mohamed Faizal Abdul-Careem Morley D. Hollenberg Craig N. Jenne Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection
description	The influenza A virus (IAV) causes a respiratory tract infection with approximately 10% of the population infected by the virus each year. Severe IAV infection is characterized by excessive inflammation and tissue pathology in the lungs. Platelet and neutrophil recruitment to the lung are involved in the pathogenesis of IAV, but the specific mechanisms involved have not been clarified. Using confocal intravital microscopy in a mouse model of IAV infection, we observed profound neutrophil recruitment, platelet aggregation, neutrophil extracellular trap (NET) production and thrombin activation within the lung microvasculature in vivo. Importantly, deficiency or antagonism of the protease-activated receptor 4 (PAR4) reduced platelet aggregation, NET production, and neutrophil recruitment. Critically, inhibition of thrombin or PAR4 protected mice from virus-induced lung tissue damage and edema. Together, these data imply thrombin-stimulated platelets play a critical role in the activation/recruitment of neutrophils, NET release and directly contribute to IAV pathogenesis in the lung.
format	article
author	Seok-Joo Kim Agostina Carestia Braedon McDonald Amanda Z. Zucoloto Heidi Grosjean Rachelle P. Davis Madison Turk Victor Naumenko Silvio Antoniak Nigel Mackman Mohamed Sarjoon Abdul-Cader Mohamed Faizal Abdul-Careem Morley D. Hollenberg Craig N. Jenne
author_facet	Seok-Joo Kim Agostina Carestia Braedon McDonald Amanda Z. Zucoloto Heidi Grosjean Rachelle P. Davis Madison Turk Victor Naumenko Silvio Antoniak Nigel Mackman Mohamed Sarjoon Abdul-Cader Mohamed Faizal Abdul-Careem Morley D. Hollenberg Craig N. Jenne
author_sort	Seok-Joo Kim
title	Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection
title_short	Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection
title_full	Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection
title_fullStr	Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection
title_full_unstemmed	Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection
title_sort	platelet-mediated net release amplifies coagulopathy and drives lung pathology during severe influenza infection
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/dca945b9c1d943fb8ab37151fffb8218
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Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection

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