TLR2 and TLR9 Synergistically Control Herpes Simplex Virus Infection in the Brain
Louise N. Sørensen,Line S. Reinert,Lene Malmgaard,Christina Bartholdy,Allan Randrup Thomsen,Søren R. Paludan +5 more
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TLDR
TLR2 and TLR9 synergistically stimulate innate antiviral activities, thereby protecting against HSV infection in the brain and recruiting but not activation of NK cells was impaired in TLR2/9−/− mice.Abstract:
Viruses are recognized by the innate immune system through pattern recognition receptors (PRRs). For instance, HSV virions and genomic DNA are recognized by TLR2 and TLR9, respectively. Although several viruses and viral components have been shown to stimulate cells through TLRs, only very few studies have defined essential roles for single TLRs in innate immune defense in vivo. This could suggest that PRRs act in concert to mount the first line of defense against virus infections. To test this hypothesis we have examined the host response of C57BL/6, TLR2(-/-), TLR9(-/-), and TLR2/9(-/-) mice toward HSV-2 infection. After a systemic infection, the cytokine serum response was markedly reduced in the double knockout mice, but only partly affected in either strain of the single knockout mice. This was supported by in vitro data showing that HSV-induced cytokine expression relayed on TLR2 and TLR9 in a cytokine- and cell type-dependent manner. With respect to the cellular response to infection, we found that recruitment but not activation of NK cells was impaired in TLR2/9(-/-) mice. Importantly, the viral load in the brain, but not liver, was significantly higher in the brain of TLR2/9(-/-) mice whereas the viral loads in organs of single knockout mice were statistically indistinguishable from C57BL/6 mice. In the brain we found that TNF-alpha and the IFN-stimulated gene CXCL9 were expressed during infection and were dependent on either TLR2 or TLR9. Thus, TLR2 and TLR9 synergistically stimulate innate antiviral activities, thereby protecting against HSV infection in the brain.read more
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Journal ArticleDOI
Regulation of innate immune responses in the brain.
TL;DR: The molecular details underlying the innate immune response in the brain during infection, injury and disease are discussed.
Journal ArticleDOI
Pattern recognition receptors and the innate immune response to viral infection
TL;DR: The role of PRRs and associated signaling pathways in detecting viral pathogens in order to evoke production of interferons and cytokines is reviewed and a greater understanding of how viruses activate PRR signaling and how this interaction shapes the anti-viral immune response is conveyed.
Journal ArticleDOI
The Role of TLR2 in Infection and Immunity
TL;DR: This review will discuss the current status of TLR2 mediated immune responses by recognition of pathogen-associated molecular patterns (PAMPS) on these organisms and emphasis on whether the inflammation induced by these responses contributes to the disease state or to protection from diseases.
Journal ArticleDOI
Toll-like receptors in antiviral innate immunity
Sandra N. Lester,Kui Li +1 more
TL;DR: The current knowledge of the roles TLRs play in antiviral innate immune responses is reviewed, examples of TLR-mediated viral recognition are discussed, and strategies used by viruses to antagonize the host antiviral inherent immune responses are described.
Journal ArticleDOI
Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential
Mark L. Hanke,Tammy Kielian +1 more
TL;DR: It is clear that TLRs can exert either beneficial or detrimental effects in the CNS, which probably depend on the context of tissue homoeostasis or pathology, therefore any potential therapeutic manipulation of TLRs will require an understanding of the signals governing specific CNS disorders to achieve tailored therapy.
References
More filters
Journal ArticleDOI
Toll-like receptor signalling
Shizuo Akira,Kiyoshi Takeda +1 more
TL;DR: Rapid progress that has recently improved the understanding of the molecular mechanisms that mediate TLR signalling is reviewed.
Journal ArticleDOI
Toll-like receptor control of the adaptive immune responses.
Akiko Iwasaki,Ruslan Medzhitov +1 more
TL;DR: Recognition of microbial infection and initiation of host defense responses is controlled by multiple mechanisms and recent studies have provided important clues about the mechanisms of TLR-mediated control of adaptive immunity orchestrated by dendritic cell populations in distinct anatomical locations.
Journal ArticleDOI
The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.
Mitsutoshi Yoneyama,Mika Kikuchi,Takashi Natsukawa,Noriaki Shinobu,Tadaatsu Imaizumi,Makoto Miyagishi,Kazunari Taira,Shizuo Akira,Takashi Fujita +8 more
TL;DR: In this article, the authors identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling.
Journal ArticleDOI
NATURAL KILLER CELLS IN ANTIVIRAL DEFENSE: Function and Regulation by Innate Cytokines
TL;DR: A detailed picture is developing of particular innate cytokines activating NK cell responses and their consorted effects in providing unique endogenous milieus promoting downstream adaptive responses, most beneficial in defense against viral infections.
Journal ArticleDOI
Innate immune recognition of viral infection.
Taro Kawai,Shizuo Akira +1 more
TL;DR: Members of the Toll-like receptor family have emerged as key sensors that recognize viral components such as nucleic acids and induce type I interferon responses via distinct signaling pathways.
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