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Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8(+) T Cell Immune Responses against West Nile Virus Infection

Interferon regulatory factor (IRF)-1 is an immunomodulatory transcription factor that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator of type I interferon (IFN)-αβ expression and the immune response to virus infections. However, this role for IR...

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Autores principales: Brien, James D., Daffis, Stephane, Lazear, Helen M., Cho, Hyelim, Suthar, Mehul S., Gale, Michael, Diamond, Michael S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164650/
https://www.ncbi.nlm.nih.gov/pubmed/21909274
http://dx.doi.org/10.1371/journal.ppat.1002230
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author Brien, James D.
Daffis, Stephane
Lazear, Helen M.
Cho, Hyelim
Suthar, Mehul S.
Gale, Michael
Diamond, Michael S.
author_facet Brien, James D.
Daffis, Stephane
Lazear, Helen M.
Cho, Hyelim
Suthar, Mehul S.
Gale, Michael
Diamond, Michael S.
author_sort Brien, James D.
collection PubMed
description Interferon regulatory factor (IRF)-1 is an immunomodulatory transcription factor that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator of type I interferon (IFN)-αβ expression and the immune response to virus infections. However, this role for IRF-1 remains controversial because altered type I IFN responses have not been systemically observed in IRF-1 (-/-) mice. To evaluate the relationship of IRF-1 and immune regulation, we assessed West Nile virus (WNV) infectivity and the host response in IRF-1 (-/-) cells and mice. IRF-1 (-/-) mice were highly vulnerable to WNV infection with enhanced viral replication in peripheral tissues and rapid dissemination into the central nervous system. Ex vivo analysis revealed a cell-type specific antiviral role as IRF-1 (-/-) macrophages supported enhanced WNV replication but infection was unaltered in IRF-1 (-/-) fibroblasts. IRF-1 also had an independent and paradoxical effect on CD8(+) T cell expansion. Although markedly fewer CD8(+) T cells were observed in naïve animals as described previously, remarkably, IRF-1 (-/-) mice rapidly expanded their pool of WNV-specific cytolytic CD8(+) T cells. Adoptive transfer and in vitro proliferation experiments established both cell-intrinsic and cell-extrinsic effects of IRF-1 on the expansion of CD8(+) T cells. Thus, IRF-1 restricts WNV infection by modulating the expression of innate antiviral effector molecules while shaping the antigen-specific CD8(+) T cell response.
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spelling pubmed-31646502011-09-09 Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8(+) T Cell Immune Responses against West Nile Virus Infection Brien, James D. Daffis, Stephane Lazear, Helen M. Cho, Hyelim Suthar, Mehul S. Gale, Michael Diamond, Michael S. PLoS Pathog Research Article Interferon regulatory factor (IRF)-1 is an immunomodulatory transcription factor that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator of type I interferon (IFN)-αβ expression and the immune response to virus infections. However, this role for IRF-1 remains controversial because altered type I IFN responses have not been systemically observed in IRF-1 (-/-) mice. To evaluate the relationship of IRF-1 and immune regulation, we assessed West Nile virus (WNV) infectivity and the host response in IRF-1 (-/-) cells and mice. IRF-1 (-/-) mice were highly vulnerable to WNV infection with enhanced viral replication in peripheral tissues and rapid dissemination into the central nervous system. Ex vivo analysis revealed a cell-type specific antiviral role as IRF-1 (-/-) macrophages supported enhanced WNV replication but infection was unaltered in IRF-1 (-/-) fibroblasts. IRF-1 also had an independent and paradoxical effect on CD8(+) T cell expansion. Although markedly fewer CD8(+) T cells were observed in naïve animals as described previously, remarkably, IRF-1 (-/-) mice rapidly expanded their pool of WNV-specific cytolytic CD8(+) T cells. Adoptive transfer and in vitro proliferation experiments established both cell-intrinsic and cell-extrinsic effects of IRF-1 on the expansion of CD8(+) T cells. Thus, IRF-1 restricts WNV infection by modulating the expression of innate antiviral effector molecules while shaping the antigen-specific CD8(+) T cell response. Public Library of Science 2011-09-01 /pmc/articles/PMC3164650/ /pubmed/21909274 http://dx.doi.org/10.1371/journal.ppat.1002230 Text en Brien et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Brien, James D.
Daffis, Stephane
Lazear, Helen M.
Cho, Hyelim
Suthar, Mehul S.
Gale, Michael
Diamond, Michael S.
Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8(+) T Cell Immune Responses against West Nile Virus Infection
title Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8(+) T Cell Immune Responses against West Nile Virus Infection
title_full Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8(+) T Cell Immune Responses against West Nile Virus Infection
title_fullStr Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8(+) T Cell Immune Responses against West Nile Virus Infection
title_full_unstemmed Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8(+) T Cell Immune Responses against West Nile Virus Infection
title_short Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8(+) T Cell Immune Responses against West Nile Virus Infection
title_sort interferon regulatory factor-1 (irf-1) shapes both innate and cd8(+) t cell immune responses against west nile virus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164650/
https://www.ncbi.nlm.nih.gov/pubmed/21909274
http://dx.doi.org/10.1371/journal.ppat.1002230
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