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

Ogolla, Pauline S.

Abstract Details

2012, Master of Sciences, Case Western Reserve University, Pathology.
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.
Carlos Subauste (Advisor)
Nicholas Ziats (Committee Chair)
Clive Hamlin (Committee Member)
Robert Petersen (Committee Member)

Recommended Citations

Citations

  • Ogolla, P. S. (2012). The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen [Master's thesis, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1341592115

    APA Style (7th edition)

  • Ogolla, Pauline. The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen. 2012. Case Western Reserve University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1341592115.

    MLA Style (8th edition)

  • Ogolla, Pauline. "The Protein Kinase Double-stranded RNA-dependent (PKR) Enhances Protection Against Disease Cause by a Non-viral Pathogen." Master's thesis, Case Western Reserve University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1341592115

    Chicago Manual of Style (17th edition)