RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice

Seasonal influenza epidemics represent a significant global health threat. The exacerbated immune response triggered by respiratory influenza virus infection causes severe pulmonary damage and contributes to substantial morbidity and mortality. Regulator of G-protein signaling 10 (RGS10) belongs to...

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Autores principales:	Faris Almutairi, Demba Sarr, Samantha L. Tucker, Kayla Fantone, Jae-Kyung Lee, Balázs Rada
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	regulator of G-protein signaling (RGS)10 G-proteins influenza A virus monocytes neutrophils lung inflammation Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/7661ed6188944f50ba6842fab49760bf
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spelling	oai:doaj.org-article:7661ed6188944f50ba6842fab49760bf2021-12-01T13:36:31ZRGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice1664-322410.3389/fimmu.2021.772288https://doaj.org/article/7661ed6188944f50ba6842fab49760bf2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.772288/fullhttps://doaj.org/toc/1664-3224Seasonal influenza epidemics represent a significant global health threat. The exacerbated immune response triggered by respiratory influenza virus infection causes severe pulmonary damage and contributes to substantial morbidity and mortality. Regulator of G-protein signaling 10 (RGS10) belongs to the RGS protein family that act as GTPase activating proteins for heterotrimeric G proteins to terminate signaling pathways downstream of G protein-coupled receptors. While RGS10 is highly expressed in immune cells, in particular monocytes and macrophages, where it has strong anti-inflammatory effects, its physiological role in the respiratory immune system has not been explored yet. Here, we show that Rgs10 negatively modulates lung immune and inflammatory responses associated with severe influenza H1N1 virus respiratory infection in a mouse model. In response to influenza A virus challenge, mice lacking RGS10 experience enhanced weight loss and lung viral titers, higher mortality and significantly faster disease onset. Deficiency of Rgs10 upregulates the levels of several proinflammatory cytokines and chemokines and increases myeloid leukocyte accumulation in the infected lung, markedly neutrophils, monocytes, and inflammatory monocytes, which is associated with more pronounced lung damage. Consistent with this, influenza-infected Rgs10-deficent lungs contain more neutrophil extracellular traps and exhibit higher neutrophil elastase activities than wild-type lungs. Overall, these findings propose a novel, in vivo role for RGS10 in the respiratory immune system controlling myeloid leukocyte infiltration, viral clearance and associated clinical symptoms following lethal influenza challenge. RGS10 also holds promise as a new, potential therapeutic target for respiratory infections.Faris AlmutairiFaris AlmutairiDemba SarrSamantha L. TuckerKayla FantoneJae-Kyung LeeBalázs RadaFrontiers Media S.A.articleregulator of G-protein signaling (RGS)10G-proteinsinfluenza A virusmonocytesneutrophilslung inflammationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	regulator of G-protein signaling (RGS)10 G-proteins influenza A virus monocytes neutrophils lung inflammation Immunologic diseases. Allergy RC581-607
spellingShingle	regulator of G-protein signaling (RGS)10 G-proteins influenza A virus monocytes neutrophils lung inflammation Immunologic diseases. Allergy RC581-607 Faris Almutairi Faris Almutairi Demba Sarr Samantha L. Tucker Kayla Fantone Jae-Kyung Lee Balázs Rada RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice
description	Seasonal influenza epidemics represent a significant global health threat. The exacerbated immune response triggered by respiratory influenza virus infection causes severe pulmonary damage and contributes to substantial morbidity and mortality. Regulator of G-protein signaling 10 (RGS10) belongs to the RGS protein family that act as GTPase activating proteins for heterotrimeric G proteins to terminate signaling pathways downstream of G protein-coupled receptors. While RGS10 is highly expressed in immune cells, in particular monocytes and macrophages, where it has strong anti-inflammatory effects, its physiological role in the respiratory immune system has not been explored yet. Here, we show that Rgs10 negatively modulates lung immune and inflammatory responses associated with severe influenza H1N1 virus respiratory infection in a mouse model. In response to influenza A virus challenge, mice lacking RGS10 experience enhanced weight loss and lung viral titers, higher mortality and significantly faster disease onset. Deficiency of Rgs10 upregulates the levels of several proinflammatory cytokines and chemokines and increases myeloid leukocyte accumulation in the infected lung, markedly neutrophils, monocytes, and inflammatory monocytes, which is associated with more pronounced lung damage. Consistent with this, influenza-infected Rgs10-deficent lungs contain more neutrophil extracellular traps and exhibit higher neutrophil elastase activities than wild-type lungs. Overall, these findings propose a novel, in vivo role for RGS10 in the respiratory immune system controlling myeloid leukocyte infiltration, viral clearance and associated clinical symptoms following lethal influenza challenge. RGS10 also holds promise as a new, potential therapeutic target for respiratory infections.
format	article
author	Faris Almutairi Faris Almutairi Demba Sarr Samantha L. Tucker Kayla Fantone Jae-Kyung Lee Balázs Rada
author_facet	Faris Almutairi Faris Almutairi Demba Sarr Samantha L. Tucker Kayla Fantone Jae-Kyung Lee Balázs Rada
author_sort	Faris Almutairi
title	RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice
title_short	RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice
title_full	RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice
title_fullStr	RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice
title_full_unstemmed	RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice
title_sort	rgs10 reduces lethal influenza infection and associated lung inflammation in mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/7661ed6188944f50ba6842fab49760bf
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RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice

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