Studies of responses to viral infection in TLR K/O mice

Data were obtained on responses to viral infections in TLR9 -/- mice, C57Bl/6 mice and IFNalpha receptor -/- mice.

Toll receptor 9 (TLR9) is an important pattern recognition receptor. It is stimulated by foreign DNA or CpG motivs.

We found that TLR9 -/- mice were very susceptible to infection with the mouse pox virus Ectromelia. In contrast to DC from C57Bl/6 mice, DC from TLR9 -/- produced little if any interferon alpha. However, MVA-BN induced IFNalpha in presence or absence of TLR9 -/-. Moreover, coinfection with MVA-BN and Ectromilia protected TLR9 -/- mice against death. Surprisingly, coinfection with MVA-BN and Ectromilia also protected IFNalpha receptor -/- mice. The data show that MVA-BN can induce potent innate immune responses able to control viral replication to allow the specific immune response to eliminate Ectromelia in immune deficient mice.

We furthermore defined that protection by using the attenuated Vaccinia virus MVA to protect mice against poxvirus infection, if used before or at the onset of infection, partially depends on the induction of the antiviral cytokines IFN- type I, but fully depends on the presence of adaptive immune responses. Importantly we were able to demonstrate that post-exposure application for up to three days of MVA rescued mousepox virus infected mice from death. This is the first demonstration of the effectiveness of post-exposure vaccination against pathogenic poxviruses.

We will explore the innate and adaptive immune elements involved in the protection.

• stimulus type
• Modified Vaccinia Ankara,
• mouse pox virus Ectromelia

• molecule type
• Toll like receptor 9,
• interferon alpha

• organism type
• Mus musculus

• experimental design type
• in vivo design experiment

• experimental factor type
• Genotype factor

created over 16 years ago (2 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF ]   [ RelFinder ]