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Increased stability of class II MHC-peptide complexes in macrophages infected with Mycobacterium avium and the examination of a novel role for Cathepsin L in the innate immune response to Francisella Novicida infection

Florence, William C.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1173298339

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Microbiology.
Macrophages serve as a critical link between the innate and adaptive immune response to intracellular pathogens. The two primary goals of this thesis were to evaluate the stability of class II MHC-peptide complexes in macrophages infected with Mycobacterium avium and to examine the roles that endocytic proteases may play in infection with Francisella novicida. We showed when class MHC class II peptides complexes are formed in the presence of Mycobacterium avium, they exhibit increased stability that is not a result of increased biosynthesis and is an endocytic event which is mediated by the ligation of innate immune receptors. The increase in stability of class II MHC-peptide complexes can be recapitulated using protease inhibitors, suggesting innate immune receptor ligation rescues class II complexes from premature degradation. Secondly, we uncovered a critical role for Cathepsin L in the innate immune response to the intracellular pathogen Francisella novicida. Mice lacking Cathepsin L are susceptible to sub-lethal infection with F. novicida, harbor increased bacterial numbers and produce increased amounts of IFNγ. To date, this is first known role for Cathepsin L in the innate immune response to any pathogen.
Paula Bryant (Advisor)
John Gunn (Other)
Abhay Satoskar (Other)
177 p.
Biology, Microbiology
MHC class II; Cathepsin L; proteases; Francisella; Mycobacterium

Recommended Citations

Citations

  • Florence, W. C. (2007). Increased stability of class II MHC-peptide complexes in macrophages infected with Mycobacterium avium and the examination of a novel role for Cathepsin L in the innate immune response to Francisella Novicida infection [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1173298339

    APA Style (7th edition)

  • Florence, William. Increased stability of class II MHC-peptide complexes in macrophages infected with Mycobacterium avium and the examination of a novel role for Cathepsin L in the innate immune response to Francisella Novicida infection. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1173298339.

    MLA Style (8th edition)

  • Florence, William. "Increased stability of class II MHC-peptide complexes in macrophages infected with Mycobacterium avium and the examination of a novel role for Cathepsin L in the innate immune response to Francisella Novicida infection." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1173298339

    Chicago Manual of Style (17th edition)

osu1173298339
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© 2007, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.