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

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 t...

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Autores principales: 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 P, Tomic-Canic, Marjana, Kirsner, Robert S, Russell, David G, Podack, Eckhard R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626811/
https://www.ncbi.nlm.nih.gov/pubmed/26402460
http://dx.doi.org/10.7554/eLife.06508
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author 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 P
Tomic-Canic, Marjana
Kirsner, Robert S
Russell, David G
Podack, Eckhard R
author_facet 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 P
Tomic-Canic, Marjana
Kirsner, Robert S
Russell, David G
Podack, Eckhard R
author_sort McCormack, Ryan M
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.06508.001
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spelling pubmed-46268112015-11-02 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 P Tomic-Canic, Marjana Kirsner, Robert S Russell, David G Podack, Eckhard R eLife Immunology 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. DOI: http://dx.doi.org/10.7554/eLife.06508.001 eLife Sciences Publications, Ltd 2015-09-24 /pmc/articles/PMC4626811/ /pubmed/26402460 http://dx.doi.org/10.7554/eLife.06508 Text en © 2015, McCormack et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology
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 P
Tomic-Canic, Marjana
Kirsner, Robert S
Russell, David G
Podack, Eckhard R
Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
title Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
title_full Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
title_fullStr Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
title_full_unstemmed Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
title_short Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
title_sort perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626811/
https://www.ncbi.nlm.nih.gov/pubmed/26402460
http://dx.doi.org/10.7554/eLife.06508
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