Editors' ChoiceImmunology

Move Over, TLR4

Sci. Signal.  17 Sep 2013:
Vol. 6, Issue 293, pp. ec220
DOI: 10.1126/scisignal.2004724

The innate immune system senses bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 (TLR4) (see the Perspective by Kagan). However, Kayagaki et al. and Hagar et al. report that the hexa-acyl lipid A component of LPS from Gram-negative 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.

N. Kayagaki, M. T. Wong, I. B. Stowe, S. R. Ramani, L. C. Gonzalez, S. Akashi-Takamura, K. Miyake, J. Zhang, W. P. Lee, A. Muszyński, L. S. Forsberg, R. W. Carlson, V. M. Dixit, Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 341, 1246–1249 (2013). [Abstract] [Full Text]

J. A. Hagar, D. A. Powell, Y. Aachoui, R. K. Ernst, E. A. Miao, Cytoplasmic LPS activates caspase-11: Implications in TLR4-independent endotoxic shock. Science 341, 1250–1253 (2013). [Abstract] [Full Text]

J. C. Kagan, Sensing endotoxins from within. Science 341, 1184–1185 (2013). [Abstract] [Full Text]