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Please use this identifier to cite or link to this item: http://hdl.handle.net/11375/22029
Title: Understanding the role of Type I Interferon in regulating the Innate Immune Response during Herpes Simplex Virus Type 2 Infection
Other Titles: Type I IFN regulates Innate Immunity during HSV-2 Infection
Authors: Lee, Amanda
Advisor: Ashkar, Ali
Department: Medical Sciences
Keywords: Mucosal immune response, Virus infection, Natural killer cells, Type I interferons
Publication Date: 2017
Abstract: Type I interferons (IFN) are a potent antiviral cytokine group that are key regulators of the immune response against virus infection. Not only does this group activate antiviral states within target cells, it can modulate the innate immune response. In the studies presented, we investigate the effects of type I IFN on the innate immune system during a mucosal vaginal virus infection, herpes simplex virus type 2 (HSV-2), a prominent sexually transmitted infection that causes genital herpes and increases risk of human immunodeficiency virus acquisition. It is well known that type I IFN is critical for natural killer (NK) cell activation. These cells contribute to the antiviral response by suppressing virus replication and aiding in the initiation of the adaptive immune response, particularly through the release of IFN-γ. In the work presented, we demonstrate that type I IFN does not act on NK cells directly for their activation, but instead activates NK cell IFN-γ production by inducing inflammatory monocytes to release IL-18, which in turn, signals NK cells to release IFN-γ during a mucosal HSV-2 infection. Rather, direct action of type I IFN on NK cells serves to negatively regulate their IFN-γ response. We also found that type I IFN was critical for suppressing virus-induced innate immunopathology during HSV-2 infection. Overall, our studies further our understanding of type I IFN and the many roles it plays during virus infection, which has become more relevant as specific therapies altering type I IFN are being used in the clinic. Further, we provide a fundamental understanding of type I IFN and its ability to shape the innate immune response to virus infection by suppressing dysregulated and immunopathological functions while promoting beneficial innate immune responses that can help fight the infection.
URI: http://hdl.handle.net/11375/22029
Appears in Collections:Open Access Dissertations and Theses

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