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Perforin-2 Protects...
Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen
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McCormack, Ryan (author)
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- Bahnan, Wael (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL, USA
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Shrestha, Niraj (author)
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Boucher, Justin (author)
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Barreto, Marcella (author)
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Barrera, Carlos M. (author)
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Dauer, Edward A. (author)
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Freitag, Nancy E. (author)
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Khan, Wasif N. (author)
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Podack, Eckhard R. (author)
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Schesser, Kurt (author)
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(creator_code:org_t)
- 2016
- 2016
- English.
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In: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 84:4, s. 1083-1091
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- The host-encoded Perforin-2 (encoded by the macrophage-expressed gene 1, Mpeg1), which possesses a pore-forming MACPF domain, reduces the viability of bacterial pathogens that reside within membrane-bound compartments. Here, it is shown that Perforin-2 also restricts the proliferation of the intracytosolic pathogen Listeria monocytogenes. Within a few hours of systemic infection, the massive proliferation of L. monocytogenes in Perforin-2(-/-) mice leads to a rapid appearance of acute disease symptoms. We go on to show in cultured Perforin-2(-/-) cells that the vacuole-to-cytosol transitioning of L. monocytogenes is greatly accelerated. Unexpectedly, we found that in Perforin-2(-/-) macrophages, Listeria-containing vacuoles quickly (<= 15 min) acidify, and that this was coincident with greater virulence gene expression, likely accounting for the more rapid translocation of L. monocytogenes to its replicative niche in the cytosol. This hypothesis was supported by our finding that a L. monocytogenes strain expressing virulence factors at a constitutively high level replicated equally well in Perforin-2(+/+) and Perforin-2(-/-) macrophages. Our findings suggest that the protective role of Perforin-2 against listeriosis is based on it limiting the intracellular replication of the pathogen. This cellular activity of Perforin-2 may derive from it regulating the acidification of Listeria-containing vacuoles, thereby depriving the pathogen of favorable intracellular conditions that promote its virulence gene activity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- NNERT G
- 1983
- JOURNAL OF EXPERIMENTAL MEDICINE
- V157
- P1483 Angelo Michael E.
- 2012
- BMC EVOLUTIONARY BIOLOGY
- V12
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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McCormack, Ryan
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Bahnan, Wael
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Shrestha, Niraj
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Boucher, Justin
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Barreto, Marcell ...
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Barrera, Carlos ...
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show more...
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Dauer, Edward A.
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Freitag, Nancy E ...
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Khan, Wasif N.
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Podack, Eckhard ...
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Schesser, Kurt
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
- Articles in the publication
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Infection and Im ...
- By the university
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Umeå University