SESSION TITLE: Chest Infections Posters I
SESSION TYPE: Original Investigation Poster
PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM
PURPOSE: RSV is the leading cause of respiratory viral infection in infants and children, yet there are few understanding about natural antiviral response during RSV infection. To identify the cellular source of type I interferon production and the primary type I interferon producer in RSV infection and to investigate which signaling pathway can be activated by RSV and drive to produce type I interferon in RSV infection.
METHODS: The cellular source of type I interferon and the primary type I interferon producer were spatiotemporally tracked by interferon-β/YFP reporter mouse and analyzed by flow cytometry in RSV stimulated BM cells and in vivo RSV infected lung cells. The interferon-β production from in vitro RSV stimulated cells was detected by ELISA. The signaling pathway for induction of type I interferon was determined by crossbreed mouse system between interferon-β/YFP reporter mouse and TLR7, MyD88 or MAVS deficient mouse. The adaptive T cell response of MyD88, or MAVS deficient mice and monocytes ablated mice were assessed in interferon-γ producing T cells and RSV specific CD8+ T cells by flow cytometer.
RESULTS: Flow cytometer analysis from in vitro RSV stimulated BM cell revealed that RSV can induce interferon-β production in plasmacytoid DCs, monocytes, and neutrophils. The spatial and kinetic analysis of the interferon-β producing cells in vivo RSV infection indicated that monocytes were rapidly recruited to inflamed lung in early phase of infection, and primarily produced interferon-β via the MyD88 mediated pathway. In monocyte ablated mice, the amount of interferon-γ and frequency of interferon-γ producing CD8+ T cells was decreased.
CONCLUSIONS: Monocytes play a pivotal role in cytotoxic T cell response as well as the primary type I interferon producer in RSV infection.
CLINICAL IMPLICATIONS: These data have significant implications in the design of vaccines and management of RSV infection. Stimulants of monocytes may provide an ideal adjuvant candidate in RSV vaccines that will confer protective immune responses.
DISCLOSURE: The following authors have nothing to disclose: Taehoon Kim, Heung Kyu Lee
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