Evaluating vaccinia virus cytokine co-expression in TLR GKO mice

Sutherland, Duncan B., Ranasinghe, Charani, Regner, Matthias, Phipps, Simon, Matthaei, Klaus I., Day, Stephanie L. and Ramshaw, Ian A. (2011) Evaluating vaccinia virus cytokine co-expression in TLR GKO mice. Immunology and Cell Biology, 89 6: 706-715. doi:10.1038/icb.2010.157

Author Sutherland, Duncan B.
Ranasinghe, Charani
Regner, Matthias
Phipps, Simon
Matthaei, Klaus I.
Day, Stephanie L.
Ramshaw, Ian A.
Title Evaluating vaccinia virus cytokine co-expression in TLR GKO mice
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
Publication date 2011-08
Year available 2010
Sub-type Article (original research)
DOI 10.1038/icb.2010.157
Volume 89
Issue 6
Start page 706
End page 715
Total pages 10
Place of publication London, Hamps, U.K.
Publisher Nature Publishing Group
Collection year 2012
Language eng
Formatted abstract
Using Toll-like receptor (TLR) and MyD88 gene knock-out (GKO) mice the effect of TLRs and MyD88 on virus replication, interferon (IFN)-β production, natural killer (NK) cell and CD8T cell responses were assessed following ectromelia virus (ECTV) and recombinant vaccinia virus (rVV) infection. The capacity for rVVs encoding cytokines to restore immune function in MyD88−/− mice was clearly demonstrated. Results showed that TLR2−/−, TLR4−/−and TLR7−/− mice survived ECTV infection whereas MyD88−/− and TLR9−/−mice, in contrast, were highly susceptible. Next, following infection with rVV, MyD88−/− mice elicited reduced serum IFN-β, NK cell and CD8T cell responses compared with wild-type mice, whereas TLR9−/− mice showed elevated CD8T cell responses. When MyD88−/−mice were infected with rVV co-expressing IFN-β these mice were able to restore IFN-β levels and CD8T cell responses but not NK cell activation. Interestingly, even though rVV co-expressing interleukin (IL)-2 enhanced NK cell activation in MyD88−/− mice, this was not associated with an antiviral effect, as observed in normal mice. Surprisingly, co-infection with rVV IL-2/rVV IL-12, but not rVV IL-2/rVV IFN-β, restored the attenuated phenotype of rVV IL-2 in MyD88−/− mice indicating that the IL-2/IL-12 combination promotes antiviral responses. Our results clearly show that the CD8T cell defect observed in MyD88−/− mice to vaccinia virus infection can be restored by rVV-encoding IFN-β demonstrating the critical role of this cytokine in T cell mediated immunity and illustrates that the model can provide an effective platform for the elucidation of cytokine immunobiology.
Keyword Toll-like receptors
CD8(+) T-cells
Dendritic cells
I interferons
Lethal encephalitis
Poxvirus infection
Adaptive immunity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Publication date: August/September 2011. Published online 21 December 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
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