ArticleProceedings of the National Academy of Sciences of the United States of America2018
Human iPSC-derived trigeminal neurons lack constitutive TLR3-dependent immunity that protects cortical neurons from HSV-1 infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 79 citations in OpenAlex.
- The cell-type-specific roles of Toll-like receptors in herpes simplex virus infection and pathogenesis.Virulence · 2026Review
- Optimization of lytic herpes simplex virus infection in human induced pluripotent stem cell-derived cortical neurones.The Journal of general virology · 2026Article
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- An Innovative "Tooth-On-Chip" Microfluidic Device Emulating the Structure and Physiology of the Dental Pulp Tissue.Advanced healthcare materials · 2026Article
- TDP-43 promotes efficient HSV-1 replication in human DRG-derived neurons.Journal of virology · 2025Article
- Antiviral responses in peripheral and brain neurons.Current opinion in immunology · 2025Review
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- Poly-IC Alleviates Nitroglycerin-Induced Migraine by Inhibiting Neuroinflammation via TLR3/TRIF Signaling Pathway.CNS neuroscience & therapeutics · 2025Article
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- Timing and Graded BMP Signalling Determines Fate of Neural Crest and Ectodermal Placode Derivatives from Pluripotent Stem Cells.Biomedicines · 2024Review
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- Cell Intrinsic Determinants of Alpha Herpesvirus Latency and Pathogenesis in the Nervous System.Viruses · 2023Review
- iPSC-derived three-dimensional brain organoid models and neurotropic viral infections.Journal of neurovirology · 2023Review
- Varicella Zoster Virus Neuronal Latency and Reactivation Modeled in Vitro.Current topics in microbiology and immunology · 2023Review
- Variations in Aspects of Neural Precursor Cell Neurogenesis in a Human Model of HSV-1 Infection.Organogenesis · 2022Article
- Anti-pruritic effect of isothiocyanates: Potential involvement of toll-like receptor 3 signaling.Pharmacology research & perspectives · 2022Review
- Review
- Global analyses of mRNA expression in human sensory neurons reveal eIF5A as a conserved target for inflammatory pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Intrinsic antiviral immunity of barrier cells revealed by an iPSC-derived blood-brain barrier cellular model.Cell reports · 2022Article
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
Herpes simplex virus type 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in Western countries. Some HSE children carry inborn errors of the Toll-like receptor 3 (TLR3)-dependent IFN-α/β- and -λ-inducing pathway. Induced pluripotent stem cell (iPSC)-derived cortical neurons with TLR3 pathway mutations are highly susceptible to HSV-1, due to impairment of cell-intrinsic TLR3-IFN immunity. In contrast, the contribution of cell-intrinsic immunity of human trigeminal ganglion (TG) neurons remains unclear. Here, we describe efficient in vitro derivation and purification of TG neurons from human iPSCs via a cranial placode intermediate. The resulting TG neurons are of sensory identity and exhibit robust responses to heat (capsaicin), cold (icilin), and inflammatory pain (ATP). Unlike control cortical neurons, both control and TLR3-deficient TG neurons were highly susceptible to HSV-1. However, pretreatment of control TG neurons with poly(I:C) induced the cells into an anti-HSV-1 state. Moreover, both control and TLR3-deficient TG neurons developed resistance to HSV-1 following pretreatment with IFN-β but not IFN-λ. These data indicate that TG neurons are vulnerable to HSV-1 because they require preemptive stimulation of the TLR3 or IFN-α/β receptors to induce antiviral immunity, whereas cortical neurons possess a TLR3-dependent constitutive resistance that is sufficient to block incoming HSV-1 in the absence of prior antiviral signals. The lack of constitutive resistance in TG neurons in vitro is consistent with their exploitation as a latent virus reservoir in vivo. Our results incriminate deficiencies in the constitutive TLR3-dependent response of cortical neurons in the pathogenesis of HSE.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.