In:
eLife, eLife Sciences Publications, Ltd, Vol. 4 ( 2015-09-24)
Abstract:
An effective defense against foreign invaders is fundamental to an organism's survival. It is likely that immunity began to develop shortly after the emergence of Earth's first single-celled organisms and a remnant of that distant past still exists in our present day immune system in the form of Perforin-2. This ancient protein has been highly conserved throughout evolution from sea sponges to humans. Some studies have suggested that Perforin-2 may have an antimicrobial role in invertebrates (including clams, mussels, and snails) and fish. However, its mechanism of killing and its role in the mammalian immune systems has remained largely unknown. McCormack et al. now report that Perforin-2 is a crucial component of host defense against a wide spectrum of infectious bacteria in both mice and humans. This was shown when mice lacking Perforin-2 died from bacterial infections that are not normally lethal. Somewhat unexpectedly, other bactericidal molecules were also found to be less effective in the absence of Perforin-2. This indicates that Perforin-2 is required for the activity of multiple aspects of the mammalian immune system. McCormack et al. demonstrated that Perforin-2 kills by punching holes in bacteria. Unlike other pore-forming proteins that are only present in specific cells, all mammalian cells can express Perforin-2. McCormack et al. also showed that when Perforin-2 is produced at optimal levels, cells are able to combat otherwise lethal, drug-resistant bacteria, including methicillin resistant Staphylococcus aureus (MRSA). This means that Perforin-2 provides a rapid self-defense mechanism for cells against bacterial invaders. The protein's dual role as a pore-forming protein and a supporter of other antibacterial molecules is unprecedented. In the future, these findings could inform the development of treatments that activate and optimize Perforin-2 production to target and eradicate bacterial infections.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.06508.001
DOI:
10.7554/eLife.06508.002
DOI:
10.7554/eLife.06508.003
DOI:
10.7554/eLife.06508.004
DOI:
10.7554/eLife.06508.005
DOI:
10.7554/eLife.06508.006
DOI:
10.7554/eLife.06508.007
DOI:
10.7554/eLife.06508.008
DOI:
10.7554/eLife.06508.009
DOI:
10.7554/eLife.06508.010
DOI:
10.7554/eLife.06508.011
DOI:
10.7554/eLife.06508.012
DOI:
10.7554/eLife.06508.013
DOI:
10.7554/eLife.06508.014
DOI:
10.7554/eLife.06508.015
DOI:
10.7554/eLife.06508.016
DOI:
10.7554/eLife.06508.017
DOI:
10.7554/eLife.06508.018
DOI:
10.7554/eLife.06508.019
DOI:
10.7554/eLife.06508.020
DOI:
10.7554/eLife.06508.021
DOI:
10.7554/eLife.06508.022
DOI:
10.7554/eLife.06508.023
DOI:
10.7554/eLife.06508.024
DOI:
10.7554/eLife.06508.025
DOI:
10.7554/eLife.06508.026
DOI:
10.7554/eLife.06508.027
DOI:
10.7554/eLife.06508.028
DOI:
10.7554/eLife.06508.029
DOI:
10.7554/eLife.06508.030
DOI:
10.7554/eLife.06508.031
DOI:
10.7554/eLife.06508.032
DOI:
10.7554/eLife.06508.033
DOI:
10.7554/eLife.06508.034
DOI:
10.7554/eLife.06508.035
DOI:
10.7554/eLife.06508.036
DOI:
10.7554/eLife.06508.037
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2015
detail.hit.zdb_id:
2687154-3
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