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Role of Granzyme B in the Susceptibility to Secondary Bacterial Infection after Viral Infection

Dhenni, Rama, B.S.

Abstract Details

2016, MS, University of Cincinnati, Medicine: Immunology.
Viral infections predispose the host to secondary unrelated viral or bacterial infections, which is best exemplified by secondary bacterial pneumonia post-influenza virus infection. In response to viral infection, host cytotoxic protease granzyme B is induced. Granzyme B expression is associated with decreased antigen presentation by dendritic cells (DCs), release of immunosuppressive TGF-beta, extracellular matrix degradation, and increased inflammatory response. Hence, we hypothesized that granzyme B is involved in the susceptibility to secondary bacterial infection after viral infection. By using a mouse model of secondary Streptococcus pneumoniae infection following primary influenza virus or lymphocytic choriomeningitis virus (LCMV) infection, we aimed to assess the role of granzyme B in the susceptibility to S. pneumoniae after viral infection. In the present study, we showed that sublethal influenza virus infection in wild-type (WT) mice induces expression of granzyme B that was detectable extracellularly and intracellularly in the lungs. Influenza-infected granzyme B-deficient mice had similar morbidity and mortality as well as viral burden compared to infected WT mice. Importantly, when we infected WT and granzyme-B deficient mice with S. pneumoniae after 10 and 14 days of influenza virus infection, both group of mice showed similar morbidity and mortality. Furthermore, lung bacterial burden in mice were similar between WT and granzyme B-deficient mice when infected with S. pneumoniae 10 days after influenza virus infection. Moreover, we showed that WT and granzyme B-deficient mice had similar susceptibility to systemic secondary S. pneumoniae infection after 10 days of sublethal LCMV infection. In conclusion, our data show that viral-induced granzyme B is not required for enhanced susceptibility to secondary S. pneumoniae infection.
Michael Jordan, M.D. (Committee Chair)
David Hildeman, Ph.D. (Committee Member)
Jonathan Katz, Ph.D. (Committee Member)
70 p.

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Citations

  • Dhenni, R. (2016). Role of Granzyme B in the Susceptibility to Secondary Bacterial Infection after Viral Infection [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460446984

    APA Style (7th edition)

  • Dhenni, Rama. Role of Granzyme B in the Susceptibility to Secondary Bacterial Infection after Viral Infection. 2016. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460446984.

    MLA Style (8th edition)

  • Dhenni, Rama. "Role of Granzyme B in the Susceptibility to Secondary Bacterial Infection after Viral Infection." Master's thesis, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460446984

    Chicago Manual of Style (17th edition)