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


O'Gorman, WE and Sampath, P and Simonds, EF and Sikorski, R and O'Malley, M and Krutzik, PO and Chen, H and Panchanathan, V and Chaudhri, G and Karupiah, G and Lewis, DB and Thorne, SH and Nolan, GP, Alternate mechanisms of initial pattern recognition drive differential immune responses to related poxviruses, Cell Host and Microbe, 8, (2) pp. 174-185. ISSN 1931-3128 (2010) [Refereed Article]

Copyright Statement

copyright 2010 Elsevier Inc.

DOI: doi:10.1016/j.chom.2010.07.008


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.

Item Details

Item Type:Refereed Article
Keywords:Poxvirus infection; pattern recognition; immune response; protection
Research Division:Biomedical and Clinical Sciences
Research Group:Medical microbiology
Research Field:Medical virology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Prevention of human diseases and conditions
UTAS Author:Karupiah, G (Associate Professor Guna Karupiah)
ID Code:143043
Year Published:2010
Web of Science® Times Cited:22
Deposited By:Medicine
Deposited On:2021-02-23
Last Modified:2021-03-30

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