Alternate mechanisms of initial pattern recognition drive differential immune responses to related poxviruses

William E. O'Gorman, Padma Sampath, Erin F. Simonds, Rachel Sikorski, Mark O'Malley, Peter O. Krutzik, Hannah Chen, Vijay Panchanathan, Geeta Chaudhri, Gunasegaran Karupiah, David B. Lewis, Steve H. Thorne, Garry P. Nolan

    Research output: Contribution to journalArticlepeer-review

    25 Citations (Scopus)

    Abstract

    Vaccinia immunization was pivotal to successful smallpox eradication. However, the early immune responses that distinguish poxvirus immunization from pathogenic infection remain unknown. To address this, we developed a strategy to map the activation of key signaling networks in vivo and applied this approach to define and compare the earliest signaling events elicited by immunizing (vaccinia) and lethal (ectromelia) poxvirus infections in mice. Vaccinia induced rapid TLR2-dependent responses, leading to IL-6 production, which then initiated STAT3 signaling in dendritic and T cells. In contrast, ectromelia did not induce TLR2 activation, and profound mouse strain-dependent responses were observed. In resistant C57BL/6 mice, the STAT1 and STAT3 pathways were rapidly activated, whereas in susceptible BALB/c mice, IL-6-dependent STAT3 activation did not occur. These data link early immune signaling events to infection outcome and suggest that activation of different pattern-recognition receptors early after infection may be important in determining vaccine efficacy.

    Original languageEnglish
    Pages (from-to)174-185
    Number of pages12
    JournalCell Host and Microbe
    Volume8
    Issue number2
    DOIs
    Publication statusPublished - 19 Aug 2010

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