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

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23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere06508
JournaleLife
Volume4
Issue numberSeptember2015
DOIs
Publication statusPublished - Sep 24 2015

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    McCormack, R. M., de Armas, L. R., Shiratsuchi, M., Fiorentino, D. G., Olsson, M. L., Lichtenheld, M. G., Morales, A., Lyapichev, K., Gonzalez, L. E., Strbo, N., Sukumar, N., Stojadinovic, O., Plano, G. V., Munson, G. P., Tomic-Canic, M., Kirsner, R. S., Russell, D. G., & Podack, E. R. (2015). Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria. eLife, 4(September2015), [e06508]. https://doi.org/10.7554/eLife.06508