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 stimulation
|
Lethality | Reference | |
|---|---|---|---|---|
| Induction of IFN-β or IFN-dependent genes (mRNA level) | Proinflammatory cytokine production (protein level) or NF-κB activation | |||
| TRIF(m) | ↓↓ | ↓↓ | R | 30 |
| TRIF (c) | ↓↓ | ↓↓ | ND | 89 |
| TRAM (c) | ↓↓ | ↓↓ | ND | 90 |
| TBK1 (c) | ↓↓ | √ (NF-κB) | ND | 60 |
| IKK-ɛ/ι (c) | ↓↓ | ND | ND | 27 |
| IRF-3 | ↓↓ | √ (mRNA level) | R | 67 |
| IFNAR1 | ND | ND | R | 36 |
| TYK2 | ↓↓ | √ (IκB degrad.) | R | 39 |
| STAT1 | ↓↓ | ND | R (±) | 39 |
| STAT2 | ND | ND | ND | 58 |
| IFN-β | ND | √ | R | 39 |
| SOCS-1 | ND | √ (IκB degrad.) | S | 22 |
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.