{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:03:26Z","timestamp":1761919406133},"reference-count":67,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2010,12,21]],"date-time":"2010-12-21T00:00:00Z","timestamp":1292889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p>Using Toll\u2010like receptor (TLR) and MyD88 gene knock\u2010out (GKO) mice the effect of TLRs and MyD88 on virus replication, interferon (IFN)\u2010\u03b2 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<jats:sup>\u2212\/\u2212<\/jats:sup> mice was clearly demonstrated. Results showed that TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>, TLR4<jats:sup>\u2212\/\u2212<\/jats:sup>and TLR7<jats:sup>\u2212\/\u2212<\/jats:sup> mice survived ECTV infection whereas MyD88<jats:sup>\u2212\/\u2212<\/jats:sup> and TLR9<jats:sup>\u2212\/\u2212<\/jats:sup>mice, in contrast, were highly susceptible. Next, following infection with rVV, MyD88<jats:sup>\u2212\/\u2212<\/jats:sup> mice elicited reduced serum IFN\u2010\u03b2, NK cell and CD8T cell responses compared with wild\u2010type mice, whereas TLR9<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed elevated CD8T cell responses. When MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>mice were infected with rVV co\u2010expressing IFN\u2010\u03b2 these mice were able to restore IFN\u2010\u03b2 levels and CD8T cell responses but not NK cell activation. Interestingly, even though rVV co\u2010expressing interleukin (IL)\u20102 enhanced NK cell activation in MyD88<jats:sup>\u2212\/\u2212<\/jats:sup> mice, this was not associated with an antiviral effect, as observed in normal mice. Surprisingly, co\u2010infection with rVV IL\u20102\/rVV IL\u201012, but not rVV IL\u20102\/rVV IFN\u2010\u03b2, restored the attenuated phenotype of rVV IL\u20102 in MyD88<jats:sup>\u2212\/\u2212<\/jats:sup> mice indicating that the IL\u20102\/IL\u201012 combination promotes antiviral responses. Our results clearly show that the CD8T cell defect observed in MyD88<jats:sup>\u2212\/\u2212<\/jats:sup> mice to vaccinia virus infection can be restored by rVV\u2010encoding IFN\u2010\u03b2 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.<\/jats:p>","DOI":"10.1038\/icb.2010.157","type":"journal-article","created":{"date-parts":[[2010,12,21]],"date-time":"2010-12-21T10:56:07Z","timestamp":1292928967000},"page":"706-715","source":"Crossref","is-referenced-by-count":14,"title":["Evaluating vaccinia virus cytokine co\u2010expression in TLR GKO mice"],"prefix":"10.1111","volume":"89","author":[{"given":"Duncan B","family":"Sutherland","sequence":"first","affiliation":[{"name":"Emerging Pathogens and Vaccines Program, The John Curtin School of Medical Research, Australian National University  Canberra Australian Capital Territory 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