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IL-12p40 and IL-18 play pivotal roles in orchestrating the cell-mediated immune response to a poxvirus infection
journal contribution
posted on 2023-05-20, 21:00 authored by Wang, Y, Chaudhri, G, Jackson, RJ, Gunasegaran KarupiahGunasegaran KarupiahA 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.
History
Publication title
Journal of ImmunologyVolume
183Issue
5Pagination
3324-3331ISSN
0022-1767Department/School
Tasmanian School of MedicinePublisher
Amer Assoc ImmunologistsPlace of publication
9650 Rockville Pike, Bethesda, USA, Md, 20814Rights statement
Copyright 2009 The American Association of Immunologists, Inc.Repository Status
- Restricted