The NLRP6 Inflammasome Recognizes Lipoteichoic Acid and Regulates Gram-Positive Pathogen Infection

Cell. 2018 Nov 29;175(6):1651-1664.e14. doi: 10.1016/j.cell.2018.09.047. Epub 2018 Nov 1.


The activator and composition of the NLRP6 inflammasome remain poorly understood. We find that lipoteichoic acid (LTA), a molecule produced by Gram-positive bacteria, binds and activates NLRP6. In response to cytosolic LTA or infection with Listeria monocytogenes, NLRP6 recruited caspase-11 and caspase-1 via the adaptor ASC. NLRP6 activation by LTA induced processing of caspase-11, which promoted caspase-1 activation and interleukin-1β (IL-1β)/IL-18 maturation in macrophages. Nlrp6-/- and Casp11-/- mice were less susceptible to L. monocytogenes infection, which was associated with reduced pathogen loads and impaired IL-18 production. Administration of IL-18 to Nlrp6-/- or Casp11-/- mice restored the susceptibility of mutant mice to L. monocytogenes infection. These results reveal a previously unrecognized innate immunity pathway triggered by cytosolic LTA that is sensed by NLRP6 and exacerbates systemic Gram-positive pathogen infection via the production of IL-18.

Keywords: IL-18; Listeria monocytogenes; NLRP6; caspase-1; caspase-11; gram-positive bacteria; inflammasome; lipoteichoic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / immunology
  • Caspases / genetics
  • Caspases / immunology
  • Caspases, Initiator
  • Immunity, Innate*
  • Inflammasomes / genetics
  • Inflammasomes / immunology*
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Lipopolysaccharides / immunology*
  • Listeria monocytogenes / immunology*
  • Listeriosis / genetics
  • Listeriosis / immunology*
  • Listeriosis / pathology
  • Mice
  • Mice, Knockout
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Teichoic Acids / immunology*


  • IL1B protein, mouse
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Lipopolysaccharides
  • Nod-like receptor pyrin domain-containing protein 6, mouse
  • Receptors, Cell Surface
  • Teichoic Acids
  • lipoteichoic acid
  • Casp4 protein, mouse
  • Caspases
  • Caspases, Initiator
  • Casp1 protein, mouse
  • Caspase 1