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As the elderly are more susceptible to #COVID19 w/ signs of lung #inflammation, here's a thread about our @virusesimmunity 2016 flu paper on #antiviral resistance, excessive lung #inflammation, & a strategy to boost disease tolerance! science.sciencemag.org/content/352/62…
First we demonstrated that monos & macs from older adults have impaired type I IFN (antiviral) & #ISG responses but intact cytokine responses after #flu infection. To probe the possible in vivo consequences of weak #IFN responses in the face of robust inflammation...
... we made a mouse model that mimicked this immune response in the elderly (Mx1+/+ mice w/ genetic deletion of tlr7, mavs). Failure to induce type I IFN led to high viral titer, 2º bacterial infection, severe lung inflammation, and death.
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