DOI: 10.1126/science.1240988 ISSN:
Cytoplasmic LPS Activates Caspase-11: Implications in TLR4-Independent Endotoxic Shock
Jon A. Hagar, Daniel A. Powell, Youssef Aachoui, Robert K. Ernst, Edward A. Miao Move Over, TLR4
The innate immune system senses bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 (TLR4) (see the Perspective by
Kagan
). However,
Kayagaki
et al.
(p
1246
, published online 25 July) and
Hagar
et al.
(p.
1250
) report that the hexa-acyl lipid A component of LPS from Gramnegative bacteria is able to access the cytoplasm and activate caspase-11 to signal immune responses independently of TLR4. Mice that lack caspase-11 are resistant to LPS-induced lethality, even in the presence of TLR4.