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PMID: 16973959 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Innate immunity against vaccinia virus is mediated by TLR2 and requires TLR-independent production of IFN-beta.

Blood ·Vol. 109 ·No. 2 ·2007-01-15 ·Pages 619-25

Zhu J, Martinez J, Huang X, Yang Y

Abstract

Vaccinia virus (VV) has been used extensively as a vaccine vehicle in the clinical application for infectious diseases and cancer. Previous studies have suggested that the unique potency of VV-based vaccine lies in its effective activation of the innate immune system. However, how VV activates innate immune pathways remains largely unknown. In this study, we showed that VV elicited innate immune response through both Toll-like receptor (TLR)-dependent and -independent pathways. The TLR pathway was mediated by TLR2 and MyD88, leading to the production of proinflammatory cytokines, whereas activation of the TLR-independent pathway resulted in the secretion of IFN-beta. More importantly, both TLR-dependent and -independent pathways were required for activating innate and adaptive immunity to VV in vivo. These findings represent the first evidence that innate immune recognition of VV is mediated by TLR2, demonstrate that one pathogen can target both TLR and non-TLR innate immune pathways to work together in achieving efficient activation of host defense, and suggest potential new strategies for the design of effective vaccines.

MeSH Terms
Animals Cytokines/biosynthesis Dendritic Cells/immunology,metabolism,virology Immunity, Innate/immunology Interferon-beta/biosynthesis,immunology,metabolism Mice Mice, Inbred C57BL Mice, Knockout Myeloid Differentiation Factor 88/metabolism Signal Transduction/immunology Toll-Like Receptor 2/physiology Vaccinia virus/immunology
Chemicals
Cytokines Myd88 protein, mouse Myeloid Differentiation Factor 88 Toll-Like Receptor 2 Interferon-beta
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zhu Jiangao
Department of Medicine, Duke University Medical Center, Box 3502, Durham, NC 27710, USA.
Martinez Jennifer
Huang Xiaopei
Yang Yiping
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-06-027136
Published
2007-01-15
Epub
2006-00-14
Pages
619-25
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1785085
Subset
IM
Grants
NCI NIH HHS · P01 CA047741 · United States
NCI NIH HHS · R01 CA111807 · United States
NCI NIH HHS · CA047741 · United States
NCI NIH HHS · CA111807 · United States
External Links
PubMed source DOI: 10.1182/blood-2006-06-027136 PMC Full Text View journal details
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