Toll-like Receptors Activate Innate and Adaptive Immunity by using Dendritic Cell-Intrinsic and -Extrinsic Mechanisms

Department of Microbiology & Immunology, University of California, San Francisco, CA, 94143, USA.
Immunity (Impact Factor: 19.75). 08/2008; 29(2):272-82. DOI: 10.1016/j.immuni.2008.05.016
Source: PubMed

ABSTRACT Toll-like receptors (TLRs) play prominent roles in initiating immune responses to infection, but their roles in particular cell types in vivo are not established. Here we report the generation of mice selectively lacking the crucial TLR-signaling adaptor MyD88 in dendritic cells (DCs). In these mice, the early production of inflammatory cytokines, especially IL-12, was substantially reduced after TLR stimulation. Whereas the innate interferon-gamma response of natural killer cells and of natural killer T cells and the Th1 polarization of antigen-specific CD4(+) T cells were severely compromised after treatment with a soluble TLR9 ligand, they were largely intact after administration of an aggregated TLR9 ligand. These results demonstrate that the physical form of a TLR ligand affects which cells can respond to it and that DCs and other innate immune cells can respond via TLRs and collaborate in promoting Th1 adaptive immune responses to an aggregated stimulus.

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Available from: Baidong Hou, Sep 01, 2015
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    • "Therefore, TLR7/TLR9 signaling can also affect pathology in a Type-I IFN independent manner. DCs that lacked the TLR-adaptor protein MyD88 showed an overall decrease in the levels of inflammatory cytokines in the spleen after TLR9 stimulation with CpG [36], [51]. Furthermore, TLR signaling by DCs also affects B cell function as MyD88 deficient DCs had significantly lower levels of IgG2a anti-nucleosome autoAbs [52]. "
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    PLoS ONE 08/2014; 9(8):e102151. DOI:10.1371/journal.pone.0102151 · 3.23 Impact Factor
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    • "Fu (National University of Singapore, Singapore; Kano et al., 2003). MyD88 flox mice were provided by A. DeFranco (University of California, San Francisco, CA; Hou et al., 2008). All these transgenic mice used backcrossed 10 times to C57/BL6 background. "
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    Journal of Experimental Medicine 04/2014; 211(5). DOI:10.1084/jem.20131314 · 13.91 Impact Factor
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    • "TLR-mediated signals play prominent roles in initiating immune responses to infection [38]. In mammalian tissues, TLRs are highly expressed by resident immune cells, including dendritic cells, tissue macrophages, and mast cells and to a lesser degree by other cell types including fibroblasts, epithelial cells, and endothelial cells [39]. Upon binding ligands, all known TLRs induce the production of inflammatory cytokines including interferon (IFN)-α, IFN-β, IL-12(p40), TNF-α, IL-6, and IL-1β, which attract innate immune cells and/or promote the initiation and polarization of adaptive immune responses [40] [41] [42]. "
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