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IL-12p40 and IL-18 play pivotal roles in orchestrating the cell-mediated immune response to a poxvirus infection

Citation

Wang, Y and Chaudhri, G and Jackson, RJ and Karupiah, G, IL-12p40 and IL-18 play pivotal roles in orchestrating the cell-mediated immune response to a poxvirus infection, Journal of Immunology, 183, (5) pp. 3324-3331. ISSN 0022-1767 (2009) [Refereed Article]


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DOI: doi:10.4049/jimmunol.0803985

Abstract

A strong cell-mediated immune response is critical for controlling viral infections and is regulated by a number of cytokines, including IL-12 and IL-18. Indeed, some viruses have evolved to specifically target these pathways to counter the host immune response. Orthopoxviruses, including ectromelia virus, encode immune evasion molecules that specifically target IL-18 and IFN-gamma. We hypothesized that IL-12 and IL-18 are pivotal for induction of IFN-gamma production and subsequent generation of an effective host response to ectromelia virus infection. In this study, we demonstrate that absence of both IL-12p40 and IL-18 resulted in increased susceptibility to infection that was associated with skewing of the cytokine response to Th2 and a reduction in NK and CTL responses. The decrease in CTL response correlated with a defect in CD8(+) T cell proliferation and lower numbers of virus-specific CD8(+) T cells. Lack of either IL-12p40 and/or IL-18 was also associated with reduced numbers of CD8(+) T cells at sites of infection and with an increase in the numbers of splenic T regulatory cells. Taken together, our data indicate that IL-12p40 and IL-18 act in concert and play an important antiviral role through the up-regulation of IFN-gamma production and cell-mediated immune responses.

Item Details

Item Type:Refereed Article
Keywords:poxvirus, cytotoxic T lymphocytes, natural killer cells, interleukins 12 and 18
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Cellular immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Prevention of human diseases and conditions
UTAS Author:Karupiah, G (Associate Professor Guna Karupiah)
ID Code:142816
Year Published:2009
Web of Science® Times Cited:40
Deposited By:Medicine
Deposited On:2021-02-12
Last Modified:2021-02-19
Downloads:0

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