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:10.7554/eLife.06508

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

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Article number	e06508
Journal	eLife
Volume	4
Issue number	September2015
DOIs	https://doi.org/10.7554/eLife.06508
State	Published - Sep 24 2015
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience
General Immunology and Microbiology
General Biochemistry, Genetics and Molecular Biology

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10.7554/eLife.06508

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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), Article e06508. https://doi.org/10.7554/eLife.06508

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, GP, Tomic-Canic, M, Kirsner, RS, 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

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

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 {\AA} 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.",

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

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AU - McCormack, Ryan M.

AU - de Armas, Lesley R.

AU - Shiratsuchi, Motoaki

AU - Fiorentino, Desiree G.

AU - Olsson, Melissa L.

AU - Lichtenheld, Mathias G.

AU - Morales, Alejo

AU - Lyapichev, Kirill

AU - Gonzalez, Louis E.

AU - Strbo, Natasa

AU - Sukumar, Neelima

AU - Stojadinovic, Olivera

AU - Plano, Gregory V.

AU - Munson, George P.

AU - Tomic-Canic, Marjana

AU - Kirsner, Robert S.

AU - Russell, David G.

AU - Podack, Eckhard R.

PY - 2015/9/24

Y1 - 2015/9/24

N2 - 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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Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria

Abstract

ASJC Scopus subject areas

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