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IL-12p40 and IL-18 Play Pivotal Roles in Orchestrating the Cell-Mediated Immune Response to a Poxvirus Infection

Wang, Yang; Chaudhri, Geeta; Jackson, Ronald; Karupiah, Gunasegaran

Description

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-γ. We hypothesized that IL-12 and IL-18 are pivotal for induction of IFN-γ production and subsequent generation of an...[Show more]

dc.contributor.authorWang, Yang
dc.contributor.authorChaudhri, Geeta
dc.contributor.authorJackson, Ronald
dc.contributor.authorKarupiah, Gunasegaran
dc.date.accessioned2015-12-08T22:33:36Z
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/1885/34748
dc.description.abstractA 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-γ. We hypothesized that IL-12 and IL-18 are pivotal for induction of IFN-γ 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-γ production and cell-mediated immune responses.
dc.publisherAmerican Association of Immunologists
dc.sourceJournal of Immunology
dc.subjectKeywords: gamma interferon; interleukin 12p40; interleukin 18; animal cell; animal experiment; animal tissue; article; CD8+ T lymphocyte; cell count; cell proliferation; cellular immunity; controlled study; correlational study; cytokine production; cytokine respons
dc.titleIL-12p40 and IL-18 Play Pivotal Roles in Orchestrating the Cell-Mediated Immune Response to a Poxvirus Infection
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume183
dc.date.issued2009
local.identifier.absfor110799 - Immunology not elsewhere classified
local.identifier.ariespublicationu6800332xPUB116
local.type.statusPublished Version
local.contributor.affiliationWang, Yang, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationChaudhri, Geeta, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationJackson, Ronald, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKarupiah, Gunasegaran, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issueonline Aug 5, 2009
local.bibliographicCitation.startpage3324
local.bibliographicCitation.lastpage3331
local.identifier.doi10.4049/jimmunol.0803985
dc.date.updated2016-02-24T11:37:39Z
local.identifier.scopusID2-s2.0-70349229500
local.identifier.thomsonID000269391400052
CollectionsANU Research Publications

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