Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Academic Article uri icon

Overview

MeSH

  • Animals
  • Caspase 1
  • Flow Cytometry
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein

MeSH Major

  • Autophagy
  • Carrier Proteins
  • DNA, Mitochondrial
  • Immunity, Innate
  • Inflammasomes

abstract

  • Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. Here we demonstrate that depletion of the autophagic proteins LC3B and beclin 1 enhanced the activation of caspase-1 and secretion of interleukin 1β (IL-1β) and IL-18. Depletion of autophagic proteins promoted the accumulation of dysfunctional mitochondria and cytosolic translocation of mitochondrial DNA (mtDNA) in response to lipopolysaccharide (LPS) and ATP in macrophages. Release of mtDNA into the cytosol depended on the NALP3 inflammasome and mitochondrial reactive oxygen species (ROS). Cytosolic mtDNA contributed to the secretion of IL-1β and IL-18 in response to LPS and ATP. LC3B-deficient mice produced more caspase-1-dependent cytokines in two sepsis models and were susceptible to LPS-induced mortality. Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity.

publication date

  • March 2011

has subject area

  • Animals
  • Autophagy
  • Carrier Proteins
  • Caspase 1
  • DNA, Mitochondrial
  • Flow Cytometry
  • Immunity, Innate
  • Inflammasomes
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3079381

Digital Object Identifier (DOI)

  • 10.1038/ni.1980

PubMed ID

  • 21151103

Additional Document Info

start page

  • 222

end page

  • 230

volume

  • 12

number

  • 3