TY - JOUR
T1 - Canonical Inflammasomes Drive IFN-γ to Prime Caspase-11 in Defense against a Cytosol-Invasive Bacterium
AU - Aachoui, Youssef
AU - Kajiwara, Yuji
AU - Leaf, Irina A.
AU - Mao, Dat
AU - Ting, Jenny P.Y.
AU - Coers, Jörn
AU - Aderem, Alan
AU - Buxbaum, Joseph D.
AU - Miao, Edward A.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/9/9
Y1 - 2015/9/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84941317034&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2015.07.016
DO - 10.1016/j.chom.2015.07.016
M3 - Article
C2 - 26320999
AN - SCOPUS:84941317034
SN - 1931-3128
VL - 18
SP - 320
EP - 332
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 3
ER -