[PDF][PDF] Canonical inflammasomes drive IFN-γ to prime caspase-11 in defense against a cytosol-invasive bacterium

Y Aachoui, Y Kajiwara, IA Leaf, D Mao, JPY Ting… - Cell host & …, 2015 - cell.com
Y Aachoui, Y Kajiwara, IA Leaf, D Mao, JPY Ting, J Coers, A Aderem, JD Buxbaum, EA Miao
Cell host & microbe, 2015cell.com
The inflammatory caspases 1 and 11 are activated in response to different agonists and act
independently to induce pyroptosis. In the context of IL-1β/IL-18 secretion, however, in vitro
studies indicate that caspase-11 acts upstream of NLRP3 and caspase-1. By contrast,
studying infection in vivo by the cytosol-invasive bacterium Burkholderia thailandensis, we
find that caspase-1 activity is required upstream of caspase-11 to control infection. Caspase-
1-activated IL-18 induces IFN-γ to prime caspase-11 and rapidly clear B. thailandensis …
Summary
The inflammatory caspases 1 and 11 are activated in response to different agonists and act independently to induce pyroptosis. In the context of IL-1β/IL-18 secretion, however, in vitro studies indicate that caspase-11 acts upstream of NLRP3 and caspase-1. By contrast, studying infection in vivo by the cytosol-invasive bacterium Burkholderia thailandensis, we find that caspase-1 activity is required upstream of caspase-11 to control infection. Caspase-1-activated IL-18 induces IFN-γ to prime caspase-11 and rapidly clear B. thailandensis infection. In the absence of IL-18, bacterial burdens persist, eventually triggering other signals that induce IFN-γ. Whereas IFN-γ was essential, endogenous type I interferons were insufficient to prime caspase-11. Although mice transgenic for caspase-4, the human ortholog of caspase-11, cleared B. thailandensis in vivo, they did not strictly require IFN-γ priming. Thus, caspase-1 provides priming signals upstream of caspase-11 but not caspase-4 during murine defense against a cytosol-invasive bacterium.
cell.com