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 Munson, Marjana Tomic-Canic, Robert Kirsner, David G. Russell, Eckhard R. Podack

Research output: Contribution to journalArticle

17 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 (US)
Article numbere06508
JournaleLife
Volume4
Issue numberSeptember2015
DOIs
StatePublished - Sep 24 2015

Fingerprint

Phagocytes
Bacteria
perforin 2
Reactive Nitrogen Species
Salmonella
Methicillin
Immune system
Pathogens
Electric fuses
Salmonella typhimurium
Methicillin-Resistant Staphylococcus aureus
Infection
Knockout Mice
Organelles
Immune System
Reactive Oxygen Species
Proteins
Tissue
Molecules
Enzymes

ASJC Scopus subject areas

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

Cite this

McCormack, R. M., de Armas, L. R., Shiratsuchi, M., Fiorentino, D. G., Olsson, M. L., Lichtenheld, M. 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

Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria. / McCormack, Ryan M.; de Armas, Lesley R.; Shiratsuchi, Motoaki; Fiorentino, Desiree G.; Olsson, Melissa L.; Lichtenheld, Mathias G; Morales, Alejo; Lyapichev, Kirill; Gonzalez, Louis E.; Strbo, Natasa; Sukumar, Neelima; Stojadinovic, Olivera; Plano, Gregory V; Munson, George; Tomic-Canic, Marjana; Kirsner, Robert; Russell, David G.; Podack, Eckhard R.

In: eLife, Vol. 4, No. September2015, e06508, 24.09.2015.

Research output: Contribution to journalArticle

McCormack, RM, de Armas, LR, Shiratsuchi, M, Fiorentino, DG, Olsson, ML, Lichtenheld, MG, Morales, A, Lyapichev, K, Gonzalez, LE, Strbo, N, Sukumar, N, Stojadinovic, O, Plano, GV, Munson, G, Tomic-Canic, M, Kirsner, R, Russell, DG & Podack, ER 2015, 'Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria', eLife, vol. 4, no. September2015, e06508. https://doi.org/10.7554/eLife.06508
McCormack RM, de Armas LR, Shiratsuchi M, Fiorentino DG, Olsson ML, Lichtenheld MG et al. Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria. eLife. 2015 Sep 24;4(September2015). e06508. https://doi.org/10.7554/eLife.06508
McCormack, Ryan M. ; de Armas, Lesley R. ; Shiratsuchi, Motoaki ; Fiorentino, Desiree G. ; Olsson, Melissa L. ; Lichtenheld, Mathias G ; Morales, Alejo ; Lyapichev, Kirill ; Gonzalez, Louis E. ; Strbo, Natasa ; Sukumar, Neelima ; Stojadinovic, Olivera ; Plano, Gregory V ; Munson, George ; Tomic-Canic, Marjana ; Kirsner, Robert ; Russell, David G. ; Podack, Eckhard R. / Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria. In: eLife. 2015 ; Vol. 4, No. September2015.
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