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. 2014 Jul 23;33(19):2171–2187. doi: 10.15252/embj.201387244

Figure 7. Genetic ablation of BID and SMAC restores immunity against Shigella infection.

Figure 7

  1. Kaplan–Meier curve of wt and SMAC−/−/OMI+/− mice infected with Shigella M90T (1 × 108 cfu) (upper panel) (wt: n = 12; SMAC−/−/OMI+/−: n = 14).
  2. Macroscopic and microscopic analysis of the liver from mice treated as in (A) (scale bar = 100 μm).
  3. Kaplan–Meier curve of wt and BID−/− mice infected with Shigella M90T (1 × 108 cfu) (wt: n = 10; BID−/−: n = 9).
  4. Macroscopic and microscopic analysis of the liver from mice treated as in (C).
  5. Primary hepatocytes isolated from wt and SMAC−/−/OMI+/− mice were infected with Shigella M90T (MOI 50). Cell death was measured at the indicated time points by trypan blue exclusion. Data are presented as mean ± SD (n = 3).
  6. Primary hepatocytes isolated from wt and BID−/− mice were infected with Shigella M90T (MOI 50). Cell death was measured at the indicated time points by trypan blue exclusion. Data are presented as mean ± SD (n = 3).
  7. Upon cytosolic appearance of Shigella, NOD1-signaling, involving RIPK2 and XIAP, is activated and promotes an inflammatory response (activation of NF-κB and IL-8 production) aiming at resolution of the bacteria. However, Shigella evolved a strategy to escape the innate immune defense by orchestrating a calpain-mediated BID-activation, which in turn potentiates the release of mitochondrial SMAC to neutralize XIAP-mediated anti-bacterial inflammatory signaling.