TABLE 1.

Summary of the biological effects, relevant to endotoxemia, observed in mice or cells deficient in genes that are centrally involved in induction of type I IFNs, downstream signaling molecules, or IFNs themselvesa

Gene KO−/−LPS stimulationLethalityReference
Induction of IFN-β or IFN-dependent genes (mRNA level)Proinflammatory cytokine production (protein level) or NF-κB activation
TRIF(m)↓↓↓↓R30
TRIF (c)↓↓↓↓ND89
TRAM (c)↓↓↓↓ND90
TBK1 (c)↓↓✓ (NF-κB)ND60
IKK-ε/ι (c)↓↓NDND27
IRF-3↓↓✓ (mRNA level)R67
IFNAR1NDNDR36
TYK2↓↓✓ (IκB degrad.)R39
STAT1↓↓NDR (±)39
STAT2NDNDND58
IFN-βNDR39
SOCS-1ND✓ (IκB degrad.)S22
  • a ↓↓, strongly decreased protein/mRNA level; ✓, inflammatory cytokine production normal; R, resistant to LPS; S, sensitive to LPS; m, mice; c, cells; ND, not done.