Direct TLR2 signaling is critical for NK cell activation and function in response to vaccinia viral infection.
Abstract
Natural killer (NK) cells play an essential role in innate immune control of poxviral
infections in vivo. However, the mechanism(s) underlying NK cell activation and function
in response to poxviruses remains poorly understood. In a mouse model of infection
with vaccinia virus (VV), the most studied member of the poxvirus family, we identified
that the Toll-like receptor (TLR) 2-myeloid differentiating factor 88 (MyD88) pathway
was critical for the activation of NK cells and the control of VV infection in vivo.
We further showed that TLR2 signaling on NK cells, but not on accessory cells such
as dendritic cells (DCs), was necessary for NK cell activation and that this intrinsic
TLR2-MyD88 signaling pathway was required for NK cell activation and played a critical
role in the control of VV infection in vivo. In addition, we showed that the activating
receptor NKG2D was also important for efficient NK activation and function, as well
as recognition of VV-infected targets. We further demonstrated that VV could directly
activate NK cells via TLR2 in the presence of cytokines in vitro and TLR2-MyD88-dependent
activation of NK cells by VV was mediated through the phosphatidylinositol 3-kinase
(PI3K)-extracellular signal-regulated kinase (ERK) pathway. Taken together, these
results represent the first evidence that intrinsic TLR signaling is critical for
NK cell activation and function in the control of a viral infection in vivo, indicate
that multiple pathways are required for efficient NK cell activation and function
in response to VV infection, and may provide important insights into the design of
effective strategies to combat poxviral infections.
Type
Journal articleSubject
AnimalsCells, Cultured
Dendritic Cells
Extracellular Signal-Regulated MAP Kinases
Interleukin-12
Interleukin-6
Killer Cells, Natural
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Myeloid Differentiation Factor 88
NK Cell Lectin-Like Receptor Subfamily K
Phosphatidylinositol 3-Kinases
Receptors, Interleukin-1
Signal Transduction
Toll-Like Receptor 2
Vaccinia
Vaccinia virus
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https://hdl.handle.net/10161/4596Published Version (Please cite this version)
10.1371/journal.ppat.1000811Publication Info
Martinez, Jennifer; Huang, Xiaopei; & Yang, Yiping (2010). Direct TLR2 signaling is critical for NK cell activation and function in response
to vaccinia viral infection. PLoS Pathog, 6(3). pp. e1000811. 10.1371/journal.ppat.1000811. Retrieved from https://hdl.handle.net/10161/4596.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Xiaopei Huang
Assistant Professor in Medicine
Yiping Yang
Professor of Medicine
The goal of Dr. Yang’s laboratory is to understand the molecular and cellular
mechanisms leading to the generation of potent and long-lasting anti-tumor immunity,
and to develop effective gene immunotherapeutic strategies for treating cancer. Furthermore,
rational pre-clinical approaches will be tested in clinical trials in patients with
Epstein-Barr virus (EBV)-related malignancies. Specifically, we focus on the following
areas: 1. Innate Immunity to Viruses. Reco
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