The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen

The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen

Bibliographic Details
Main Author: Ogolla, Pauline S.
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2012
Subjects:
Immunology
PKR
non-viral pathogen
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1341592115
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case13415921152021-08-03T05:34:43Z The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen Ogolla, Pauline S. Immunology PKR non-viral pathogen PKR is well characterized for its function in antiviral immunity. Using Toxoplasma gondii, we examined if PKR promotes resistance to disease caused by a non-viral pathogen. PKR-/- mice exhibited higher parasite load and worsened histopathology in the brain and eye. Macrophages/microglia with defective PKR signaling were unable to kill the parasite in response to CD40 stimulation. The TRAF6 but not the TRAF2,3 binding sites of CD40 was required for PKR phosphorylation through CD40 ligation. TRAF6 co-immunoprecipitated with PKR upon CD40 ligation. TRAF6-PKR interaction appeared to be indirect since knock-down of TRAF2 inhibited TRAF6-PKR co-immunoprecipitation. PKR was required for accumulation LC3 around the parasite, vacuole-lysosomal fusion and killing of T. gondii in CD40-activated cells. Thus, we identified PKR as a promoter of protection against disease caused by a non-viral pathogen. PKR is activated by CD40 via TRAF6 and TRAF2 and PKR links CD40-TRAF signaling and stimulation of the autophagy pathway. 2012-08-27 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1341592115 http://rave.ohiolink.edu/etdc/view?acc_num=case1341592115 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Immunology
PKR
non-viral pathogen
spellingShingle Immunology
PKR
non-viral pathogen
Ogolla, Pauline S.
The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen
author Ogolla, Pauline S.
author_facet Ogolla, Pauline S.
author_sort Ogolla, Pauline S.
title The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen
title_short The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen
title_full The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen
title_fullStr The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen
title_full_unstemmed The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen
title_sort protein kinase double-stranded rna-dependent (pkr) enhances protection against disease cause by a non-viral pathogen
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2012
url http://rave.ohiolink.edu/etdc/view?acc_num=case1341592115
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AT ogollapaulines proteinkinasedoublestrandedrnadependentpkrenhancesprotectionagainstdiseasecausebyanonviralpathogen
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