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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.751341/full |
| _version_ | 1830382311595573248 |
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| author | Pamela J. Lincez Iryna Shanina Marc S. Horwitz |
| author_facet | Pamela J. Lincez Iryna Shanina Marc S. Horwitz |
| author_sort | Pamela J. Lincez |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T10:03:55Z |
| format | Article |
| id | doaj.art-782c50c9bc7b4bb7a0443c4be3578052 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T10:03:55Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-782c50c9bc7b4bb7a0443c4be35780522022-12-21T19:44:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.751341751341Changes in MDA5 and TLR3 Sensing of the Same Diabetogenic Virus Result in Different Autoimmune Disease OutcomesPamela J. Lincez0Iryna Shanina1Marc S. Horwitz2Michael Smith Laboratories, The University of British Columbia, Vancouver, BC, CanadaDepartment of Microbiology & Immunology, Life Sciences Institute, The University of British Columbia, Vancouver, BC, CanadaDepartment of Microbiology & Immunology, Life Sciences Institute, The University of British Columbia, Vancouver, BC, CanadaSeemingly 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.751341/fullautoimmunitydiabetesinterferonMDA5TLR3coxsackievirus |
| spellingShingle | 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 Frontiers in Immunology autoimmunity diabetes interferon MDA5 TLR3 coxsackievirus |
| title | 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_short | 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 |
| topic | autoimmunity diabetes interferon MDA5 TLR3 coxsackievirus |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.751341/full |
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