The NLRP6 Inflammasome Recognizes Lipoteichoic Acid and Regulates Gram-Positive Pathogen Infection.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30392956.
- Also identified by DOI 10.1016/j.cell.2018.09.047 and PMC identifier 6294477.
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Abstract
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<sup>-/-</sup> and Casp11<sup>-/-</sup> 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<sup>-/-</sup> or Casp11<sup>-/-</sup> 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.
Medical subject headings
- Immunity, Innate
- Inflammasomes
- Lipopolysaccharides
- Listeria monocytogenes
- Listeriosis
- Receptors, Cell Surface
- Teichoic Acids