RNA and β-hemolysin of group B Streptococcus induce interleukin-1β (IL-1β) by activating NLRP3 inflammasomes in mouse macrophages

J Biol Chem. 2014 May 16;289(20):13701-5. doi: 10.1074/jbc.C114.548982. Epub 2014 Apr 1.

Abstract

The inflammatory cytokine IL-1β is critical for host responses against many human pathogens. Here, we define Group B Streptococcus (GBS)-mediated activation of the Nod-like receptor-P3 (NLRP3) inflammasome in macrophages. NLRP3 activation requires GBS expression of the cytolytic toxin, β-hemolysin, lysosomal acidification, and leakage. These processes allow the interaction of GBS RNA with cytosolic NLRP3. The present study supports a model in which GBS RNA, along with lysosomal components including cathepsins, leaks out of lysosomes and interacts with NLRP3 to induce IL-1β production.

Keywords: Cell Signaling; Immunology; Innate Immunity; Interleukin; RNA.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Hemolysin Proteins / metabolism*
  • Humans
  • Inflammasomes / metabolism*
  • Interleukin-1beta / biosynthesis*
  • Interleukin-1beta / metabolism
  • Lysosomes / metabolism
  • Lysosomes / microbiology
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Macrophages / microbiology
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Phagosomes / metabolism
  • Phagosomes / microbiology
  • RNA, Bacterial / metabolism*
  • Streptococcus agalactiae / metabolism
  • Streptococcus agalactiae / physiology*

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Hemolysin Proteins
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Nlrp3 protein, mouse
  • RNA, Bacterial
  • streptococcal group B hemolysin