Aged IRF3-KO Mice are Protected from Sepsis

Dinesh G Goswami,1 Wendy E Walker1,2 1Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA; 2Graduate School of Biomedical Sciences, Texas Tech Universi...

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Autores principales:	Goswami DG, Walker WE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	septicemia clp interferon regulatory factor 3 aging mice sex Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2b3668c82abf4916ae7f88189ddce026
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spelling	oai:doaj.org-article:2b3668c82abf4916ae7f88189ddce0262021-12-02T17:54:55ZAged IRF3-KO Mice are Protected from Sepsis1178-7031https://doaj.org/article/2b3668c82abf4916ae7f88189ddce0262021-11-01T00:00:00Zhttps://www.dovepress.com/aged-irf3-ko-mice-are-protected-from-sepsis-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Dinesh G Goswami,1 Wendy E Walker1,2 1Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA; 2Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USACorrespondence: Wendy E WalkerTexas Tech University Health Sciences Center El Paso, 5001 El Paso Drive, El Paso, TX, 79905, USATel +1-915-215-4268Fax +1-915- 783-1253Email wendy.walker@ttuhsc.eduPurpose: Sepsis is a leading cause of hospital admissions and deaths. Older adults (> 65 years) are particularly susceptible to sepsis and experience higher morbidity and mortality rates than younger people. We previously showed that interferon regulatory factor 3 (IRF3) contributes to sepsis pathogenesis in young mice subject to cecal ligation and puncture (CLP). In this study, we investigated if IRF3 contributes to sepsis in the context of aging.Methods: Sepsis was induced in aged wild-type (WT) and IRF3-knock-out (KO) mice, using a clinically-relevant CLP-sepsis model including fluids and antibiotics. Animal survival, disease score and hypothermia were evaluated as indicators of sepsis pathogenesis. Serum cytokines and serum enzymes indicative of organ damage were also measured.Results: Aged WT mice were highly susceptible to sepsis (90% mortality). In comparison, aged IRF3-KO mice were significantly protected (20% mortality). Aged IRF3-KO mice showed a lower disease score and reduced hypothermia following CLP, compared to WT mice. Serum cytokines interleukin (IL)-6, IL-12/23p40 and macrophage chemoattractant protein (MCP)-1, and creatinine kinase (CK) were lower in aged IRF3-KO septic mice compared to WT counterparts. Aged male mice were found to be more susceptible to sepsis compared to females. Female mice, however, produced higher levels of serum cytokines and CK.Conclusion: These results demonstrate that IRF3 plays a detrimental role in sepsis in aged mice and highlight the impact of biological sex.Keywords: septicemia, CLP, interferon regulatory factor 3, aging, mice, sexGoswami DGWalker WEDove Medical Pressarticlesepticemiaclpinterferon regulatory factor 3agingmicesexPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 5757-5767 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	septicemia clp interferon regulatory factor 3 aging mice sex Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	septicemia clp interferon regulatory factor 3 aging mice sex Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Goswami DG Walker WE Aged IRF3-KO Mice are Protected from Sepsis
description	Dinesh G Goswami,1 Wendy E Walker1,2 1Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA; 2Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USACorrespondence: Wendy E WalkerTexas Tech University Health Sciences Center El Paso, 5001 El Paso Drive, El Paso, TX, 79905, USATel +1-915-215-4268Fax +1-915- 783-1253Email wendy.walker@ttuhsc.eduPurpose: Sepsis is a leading cause of hospital admissions and deaths. Older adults (> 65 years) are particularly susceptible to sepsis and experience higher morbidity and mortality rates than younger people. We previously showed that interferon regulatory factor 3 (IRF3) contributes to sepsis pathogenesis in young mice subject to cecal ligation and puncture (CLP). In this study, we investigated if IRF3 contributes to sepsis in the context of aging.Methods: Sepsis was induced in aged wild-type (WT) and IRF3-knock-out (KO) mice, using a clinically-relevant CLP-sepsis model including fluids and antibiotics. Animal survival, disease score and hypothermia were evaluated as indicators of sepsis pathogenesis. Serum cytokines and serum enzymes indicative of organ damage were also measured.Results: Aged WT mice were highly susceptible to sepsis (90% mortality). In comparison, aged IRF3-KO mice were significantly protected (20% mortality). Aged IRF3-KO mice showed a lower disease score and reduced hypothermia following CLP, compared to WT mice. Serum cytokines interleukin (IL)-6, IL-12/23p40 and macrophage chemoattractant protein (MCP)-1, and creatinine kinase (CK) were lower in aged IRF3-KO septic mice compared to WT counterparts. Aged male mice were found to be more susceptible to sepsis compared to females. Female mice, however, produced higher levels of serum cytokines and CK.Conclusion: These results demonstrate that IRF3 plays a detrimental role in sepsis in aged mice and highlight the impact of biological sex.Keywords: septicemia, CLP, interferon regulatory factor 3, aging, mice, sex
format	article
author	Goswami DG Walker WE
author_facet	Goswami DG Walker WE
author_sort	Goswami DG
title	Aged IRF3-KO Mice are Protected from Sepsis
title_short	Aged IRF3-KO Mice are Protected from Sepsis
title_full	Aged IRF3-KO Mice are Protected from Sepsis
title_fullStr	Aged IRF3-KO Mice are Protected from Sepsis
title_full_unstemmed	Aged IRF3-KO Mice are Protected from Sepsis
title_sort	aged irf3-ko mice are protected from sepsis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/2b3668c82abf4916ae7f88189ddce026
work_keys_str_mv	AT goswamidg agedirf3komiceareprotectedfromsepsis AT walkerwe agedirf3komiceareprotectedfromsepsis
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Aged IRF3-KO Mice are Protected from Sepsis

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