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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. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Brien, JD, Daffis, S, Lazear, HM, Cho, H, Suthar, MS, Gale, M, Diamond, MS |
Journal | PLoS Pathog |
Volume | 7 |
Issue | 9 |
Pagination | e1002230 |
Date Published | 2011 Sep |
ISSN | 1553-7374 |
Keywords | Adaptive Immunity, Animals, B-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Central Nervous System, Immunity, Innate, Interferon Regulatory Factor-1, Interferon-beta, Interferon-gamma, Macrophages, Mice, Mice, Inbred C57BL, West Nile Fever, West Nile virus |
Abstract | 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. |
DOI | 10.1371/journal.ppat.1002230 |
Alternate Journal | PLoS Pathog. |
PubMed ID | 21909274 |