TY - JOUR
T1 - Alternate mechanisms of initial pattern recognition drive differential immune responses to related poxviruses
AU - O'Gorman, William E.
AU - Sampath, Padma
AU - Simonds, Erin F.
AU - Sikorski, Rachel
AU - O'Malley, Mark
AU - Krutzik, Peter O.
AU - Chen, Hannah
AU - Panchanathan, Vijay
AU - Chaudhri, Geeta
AU - Karupiah, Gunasegaran
AU - Lewis, David B.
AU - Thorne, Steve H.
AU - Nolan, Garry P.
PY - 2010/8/19
Y1 - 2010/8/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77956315094&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2010.07.008
DO - 10.1016/j.chom.2010.07.008
M3 - Article
SN - 1931-3128
VL - 8
SP - 174
EP - 185
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -