Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes

Seemingly redundant in function, melanoma differentiation-associated protein 5 (MDA5) and toll-like receptor- 3 (TLR3) both sense RNA viruses and induce type I interferon (IFN-I). Herein, we demonstrate that changes in sensing of the same virus by MDA5 and TLR3 can lead to distinct signatures of IFN...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Pamela J. Lincez, Iryna Shanina, Marc S. Horwitz
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	autoimmunity diabetes interferon MDA5 TLR3 coxsackievirus Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/782c50c9bc7b4bb7a0443c4be3578052
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:782c50c9bc7b4bb7a0443c4be3578052
record_format	dspace
spelling	oai:doaj.org-article:782c50c9bc7b4bb7a0443c4be35780522021-11-05T06:46:02ZChanges in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes1664-322410.3389/fimmu.2021.751341https://doaj.org/article/782c50c9bc7b4bb7a0443c4be35780522021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.751341/fullhttps://doaj.org/toc/1664-3224Seemingly redundant in function, melanoma differentiation-associated protein 5 (MDA5) and toll-like receptor- 3 (TLR3) both sense RNA viruses and induce type I interferon (IFN-I). Herein, we demonstrate that changes in sensing of the same virus by MDA5 and TLR3 can lead to distinct signatures of IFN-α and IFN-ß resulting in different disease outcomes. Specifically, infection with a diabetogenic islet β cell-tropic strain of coxsackievirus (CB4) results in diabetes protection under reduced MDA5 signaling conditions while reduced TLR3 function retains diabetes susceptibility. Regulating the induction of IFN-I at the site of virus infection creates a local site of interferonopathy leading to loss of T cell regulation and induction of autoimmune diabetes. We have not demonstrated another way to prevent T1D in the NOD mouse, rather we believe this work has provided compounding evidence for a specific control of IFN-I to drive a myriad of responses ranging from virus clearance to onset of autoimmune diabetes.Pamela J. LincezIryna ShaninaMarc S. HorwitzFrontiers Media S.A.articleautoimmunitydiabetesinterferonMDA5TLR3coxsackievirusImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autoimmunity diabetes interferon MDA5 TLR3 coxsackievirus Immunologic diseases. Allergy RC581-607
spellingShingle	autoimmunity diabetes interferon MDA5 TLR3 coxsackievirus Immunologic diseases. Allergy RC581-607 Pamela J. Lincez Iryna Shanina Marc S. Horwitz Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes
description	Seemingly redundant in function, melanoma differentiation-associated protein 5 (MDA5) and toll-like receptor- 3 (TLR3) both sense RNA viruses and induce type I interferon (IFN-I). Herein, we demonstrate that changes in sensing of the same virus by MDA5 and TLR3 can lead to distinct signatures of IFN-α and IFN-ß resulting in different disease outcomes. Specifically, infection with a diabetogenic islet β cell-tropic strain of coxsackievirus (CB4) results in diabetes protection under reduced MDA5 signaling conditions while reduced TLR3 function retains diabetes susceptibility. Regulating the induction of IFN-I at the site of virus infection creates a local site of interferonopathy leading to loss of T cell regulation and induction of autoimmune diabetes. We have not demonstrated another way to prevent T1D in the NOD mouse, rather we believe this work has provided compounding evidence for a specific control of IFN-I to drive a myriad of responses ranging from virus clearance to onset of autoimmune diabetes.
format	article
author	Pamela J. Lincez Iryna Shanina Marc S. Horwitz
author_facet	Pamela J. Lincez Iryna Shanina Marc S. Horwitz
author_sort	Pamela J. Lincez
title	Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes
title_short	Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes
title_full	Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes
title_fullStr	Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes
title_full_unstemmed	Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes
title_sort	changes in mda5 and tlr3 sensing of the same diabetogenic virus result in different autoimmune disease outcomes
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/782c50c9bc7b4bb7a0443c4be3578052
work_keys_str_mv	AT pamelajlincez changesinmda5andtlr3sensingofthesamediabetogenicvirusresultindifferentautoimmunediseaseoutcomes AT irynashanina changesinmda5andtlr3sensingofthesamediabetogenicvirusresultindifferentautoimmunediseaseoutcomes AT marcshorwitz changesinmda5andtlr3sensingofthesamediabetogenicvirusresultindifferentautoimmunediseaseoutcomes
_version_	1718444476756656128

Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease Outcomes

Ejemplares similares