مورد إلكتروني

Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen

التفاصيل البيبلوغرافية
العنوان: Perforin-2 Protects Host Cells and Mice by Restricting the Vacuole to Cytosol Transitioning of a Bacterial Pathogen
بيانات النشر: Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten) Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL, USA 2016
تفاصيل مُضافة: McCormack, Ryan
Bahnan, Wael
Shrestha, Niraj
Boucher, Justin
Barreto, Marcella
Barrera, Carlos M.
Dauer, Edward A.
Freitag, Nancy E.
Khan, Wasif N.
Podack, Eckhard R.
Schesser, Kurt
نوع الوثيقة: Electronic Resource
مستخلص: 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.
مصطلحات الفهرس: NNERT G, 1983, JOURNAL OF EXPERIMENTAL MEDICINE, V157, P1483 Angelo Michael E., 2012, BMC EVOLUTIONARY BIOLOGY, V12, Infectious Medicine, Infektionsmedicin, Article in journal, info:eu-repo/semantics/article, text
DOI: 10.1128.IAI.01434-15
URL: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-123079
Infection and Immunity, 0019-9567, 2016, 84:4, s. 1083-1091
الإتاحة: Open access content. Open access content
info:eu-repo/semantics/openAccess
ملاحظة: application/pdf
English
أرقام أخرى: UPE oai:DiVA.org:umu-123079
doi:10.1128/IAI.01434-15
PMID 26831467
ISI:000377103600020
Scopus 2-s2.0-84962859558
957072702
المصدر المساهم: UPPSALA UNIV LIBR
From OAIster®, provided by the OCLC Cooperative.
رقم الأكسشن: edsoai.ocn957072702
قاعدة البيانات: OAIster