Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782398168822972416 |
---|---|
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 |
format | Online Article Text |
id | pubmed-4626811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT mccormackryanm perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT dearmaslesleyr perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT shiratsuchimotoaki perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT fiorentinodesireeg perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT olssonmelissal perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT lichtenheldmathiasg perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT moralesalejo perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT lyapichevkirill perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT gonzalezlouise perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT strbonatasa perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT sukumarneelima perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT stojadinovicolivera perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT planogregoryv perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT munsongeorgep perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT tomiccanicmarjana perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT kirsnerroberts perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT russelldavidg perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria AT podackeckhardr perforin2isessentialforintracellulardefenseofparenchymalcellsandphagocytesagainstpathogenicbacteria |