Artificial Loading of ASC Specks with Cytosolic Antigens

PLoS One. 2015 Aug 10;10(8):e0134912. doi: 10.1371/journal.pone.0134912. eCollection 2015.

Abstract

Inflammasome complexes form upon interaction of Nod Like Receptor (NLR) proteins with pathogen associated molecular patterns (PAPMS) inside the cytosol. Stimulation of a subset of inflammasome receptors including NLRP3, NLRC4 and AIM2 triggers formation of the micrometer-sized spherical supramolecular complex called the ASC speck. The ASC speck is thought to be the platform of inflammasome activity, but the reason why a supramolecular complex is preferred against oligomeric platforms remains elusive. We observed that a set of cytosolic proteins, including the model antigen ovalbumin, tend to co-aggregate on the ASC speck. We suggest that co-aggregation of antigenic proteins on the ASC speck during intracellular infection might be instrumental in antigen presentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation*
  • Antigens / chemistry
  • CARD Signaling Adaptor Proteins / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Caspase 1 / metabolism
  • Cell Differentiation
  • Cytoskeleton / metabolism
  • Cytosol / metabolism
  • DNA-Binding Proteins / metabolism*
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Inflammasomes / metabolism*
  • Inflammation
  • Macrophages / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Ovalbumin / chemistry
  • Proteasome Endopeptidase Complex / metabolism
  • Tetradecanoylphorbol Acetate / chemistry
  • Ubiquitin / metabolism

Substances

  • AIM2 protein, human
  • Antigens
  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRC4 protein, human
  • NLRP3 protein, human
  • Ubiquitin
  • Green Fluorescent Proteins
  • Ovalbumin
  • Caspase 1
  • Proteasome Endopeptidase Complex
  • Tetradecanoylphorbol Acetate

Grants and funding

This project was supported by the European Molecular Biology Organization Installation Grant (EMBO-SDIG 1468) and Boğaziçi University Research Fund (BAP-6526 and BAP-TUG 8400 Grants) Grant to N.Ö.