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Dissertation__Resiliac FNL.pdf (16.49 MB)

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Low dose of lipopolysaccharide protects mice from lethal paramyxovirus infection and post-viral airway disease

Resiliac, Jenny
http://rave.ohiolink.edu/etdc/view?acc_num=osu1669930018254415

Abstract Details

2022, Doctor of Philosophy, Ohio State University, Biomedical Sciences.
Everyone experiences a respiratory infection in their lifetime. Respiratory diseases are among the leading causes of disability and death in the world [1]. Infection with viruses such as influenza and respiratory syncytial virus contribute significantly to morbidity and mortality globally and to high health care costs [1]. Therefore, understanding the antiviral immune response is critical for innovating therapeutic interventions that can relieve the morbidity and mortality burden associated with respiratory viral infections. Our study demonstrates that low dose lipopolysaccharide (LPS) is protective against a severe respiratory viral infection. This protection depends upon macrophages, but not neutrophils. LPS, which binds to toll-like receptor 4 (TLR4) to induce the nuclear factor-kappa- light- chain enhancer of activated B cells (NF-kB ) pathway through the adaptor protein myeloid differentiation 88 (MyD88), can stimulate increased production of antiviral type I interferons (IFN) [2]. Therefore, we further determined the role of the TLR4/MyD88 pathway in the survival advantage conferred by LPS along with the requirement for type I IFN. Our results suggest that the low dose LPS induced protection is mediated through type I interferon, TLR4 and MyD88, as mice genetically unable to signal through these molecules fail to gain a survival advantage with LPS pretreatment. Here, we determined the innate immune cells that are playing critical roles during a severe respiratory infection to mediate survival, the role of type I IFN in LPS mediated protection from the severe respiratory viral infection, identified a novel roles for the TLR4-MyD88 axis in mediating survival from respiratory viral infection. This study is the first to our knowledge to demonstrate a protective effect of low dose endotoxin exposure (LPS) on the murine antiviral immune response using a native murine virus and a normally lethal viral infection.
Mitchell H. Grayson (Advisor)
Richard Robinson (Committee Member)
Prosper Boyaka (Committee Member)
Michael T. Bailey (Committee Member)
176 p.
Biomedical Research
Lipopolysaccharide; Sendai virus; innate immune response; Toll-like receptor 4; MyD88; Type I interferons; rodents

Recommended Citations

Citations

  • Resiliac, J. (2022). Low dose of lipopolysaccharide protects mice from lethal paramyxovirus infection and post-viral airway disease [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1669930018254415

    APA Style (7th edition)

  • Resiliac, Jenny. Low dose of lipopolysaccharide protects mice from lethal paramyxovirus infection and post-viral airway disease. 2022. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1669930018254415.

    MLA Style (8th edition)

  • Resiliac, Jenny. "Low dose of lipopolysaccharide protects mice from lethal paramyxovirus infection and post-viral airway disease." Doctoral dissertation, Ohio State University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=osu1669930018254415

    Chicago Manual of Style (17th edition)

osu1669930018254415
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This open access ETD is published by The Ohio State University and OhioLINK.