eLife (Sep 2015)

Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria

  • Ryan M McCormack,
  • Lesley R de Armas,
  • Motoaki Shiratsuchi,
  • Desiree G Fiorentino,
  • Melissa L Olsson,
  • Mathias G Lichtenheld,
  • Alejo Morales,
  • Kirill Lyapichev,
  • Louis E Gonzalez,
  • Natasa Strbo,
  • Neelima Sukumar,
  • Olivera Stojadinovic,
  • Gregory V Plano,
  • George P Munson,
  • Marjana Tomic-Canic,
  • Robert S Kirsner,
  • David G Russell,
  • Eckhard R Podack

DOI
https://doi.org/10.7554/eLife.06508
Journal volume & issue
Vol. 4

Abstract

Read online

Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles- that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100 Å pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.

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