Nucleic Acid Sensing by Toll-Like Receptors in the Endosomal Compartment

Miyake, Kensuke; Shibata, Takuma; Fukui, Ryutaro; Sato, Ryota; Saitoh, Shin-Ichiroh; Murakami, Yusuke

doi:10.3389/fimmu.2022.941931

Cited by 14 publications

(12 citation statements)

References 79 publications

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“…The resulting signaling cascades lead to the production of type I interferons (IFN) and pro-inflammatory cytokines [ 24 ]. Although the innate response has an adjuvant effect which can promote the specific immune response, it can also induce RNA degradation and thereby reduce antigen expression [ 132 ].…”

Section: Sarna Vaccine Candidates and The Induction Of Innate Immune ...mentioning

confidence: 99%

Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development

Schmidt

Schnierle

2023

Pathogens

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The present use of mRNA vaccines against COVID-19 has shown for the first time the potential of mRNA vaccines for infectious diseases. Here we will summarize the current knowledge about improved mRNA vaccines, i.e., the self-amplifying mRNA (saRNA) vaccines. This approach may enhance antigen expression by amplification of the antigen-encoding RNA. RNA design, RNA delivery, and the innate immune responses induced by RNA will be reviewed.

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Section: Sarna Vaccine Candidates and The Induction Of Innate Immune ...mentioning

confidence: 99%

Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development

Schmidt

Schnierle

2023

Pathogens

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“…Each TLR has a precise threshold which avoids sensing of self-nucleic acids and, consequently, decreases chances for autoimmune disease development. On the other hand, the threshold must not be too high so that it would not activate the immune response when needed [ 51 ]. TLR3 recognises double-stranded RNA (dsRNA) and, contrary to other NA-sensing TLRs, is present both on the cell surface and on the endosomal membrane of macrophages and mast cells [ 52 ].…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Role of TLRs in HIV-1 Infection and Potential of TLR Agonists in HIV-1 Vaccine Development and Treatment Strategies

et al. 2023

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Toll-like receptors (TLRs), as a family of pattern recognition receptors, play an important role in the recognition of HIV-1 molecular structures by various cells of the innate immune system, but also provide a functional association with subsequent mechanisms of adaptive immunity. TLR7 and TLR8 play a particularly important role in the innate immune response to RNA viruses due to their ability to recognise GU-rich single-stranded RNA molecules and subsequently activate intracellular signalling pathways resulting in expression of genes coding for various biological response modifiers (interferons, proinflammatory cytokines, chemokines). The aim of this review is to summarise the most recent knowledge on the role of TLRs in the innate immune response to HIV-1 and the role of TLR gene polymorphisms in the biology and in the clinical aspects of HIV infections. In addition, the role of TLR agonists as latency reversing agents in research to treat HIV infections and as immunomodulators in HIV vaccine research will be discussed.

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“…TLR9 is present in the endoplasmic reticulum (ER), during normal physiologic stages. However, when cytosolic cytosine-phosphate-guanine (CpG)-DNAs or self-DNA enter the endosome or endolysosome, TLR9 migrates to these organelles and recognizes them as essential DAMPs [ 111 , 112 ]. In order to cause inflammation and inflammatory diseases, the TLR9 activation induces a myeloid differentiation primary response 88 (MyD88)-dependent downstream signaling pathway that activates the IRF3-based type1-interferon production and NF-kB-mediated pro-inflammatory cytokine production [ 113 ].…”

Section: Recognition and Immunomodulatory Role Of Cell-free Dnamentioning

confidence: 99%

Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors

Műzes¹,

Barta²,

Szabó³

et al. 2022

Biomedicines

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The basic function of the immune system is the protection of the host against infections, along with the preservation of the individual antigenic identity. The process of self-tolerance covers the discrimination between self and foreign antigens, including proteins, nucleic acids, and larger molecules. Consequently, a broken immunological self-tolerance results in the development of autoimmune or autoinflammatory disorders. Immunocompetent cells express pattern-recognition receptors on their cell membrane and cytoplasm. The majority of endogenous DNA is located intracellularly within nuclei and mitochondria. However, extracellular, cell-free DNA (cfDNA) can also be detected in a variety of diseases, such as autoimmune disorders and malignancies, which has sparked interest in using cfDNA as a possible biomarker. In recent years, the widespread use of liquid biopsies and the increasing demand for screening, as well as monitoring disease activity and therapy response, have enabled the revival of cfDNA research. The majority of studies have mainly focused on the function of cfDNA as a biomarker. However, research regarding the immunological consequences of cfDNA, such as its potential immunomodulatory or therapeutic benefits, is still in its infancy. This article discusses the involvement of various DNA-sensing receptors (e.g., absent in melanoma-2; Toll-like receptor 9; cyclic GMP–AMP synthase/activator of interferon genes) in identifying host cfDNA as a potent danger-associated molecular pattern. Furthermore, we aim to summarize the results of the experimental studies that we recently performed and highlight the immunomodulatory capacity of cfDNA, and thus, the potential for possible therapeutic consideration.

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Nucleic Acid Sensing by Toll-Like Receptors in the Endosomal Compartment

Cited by 14 publications

References 79 publications

Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development

Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development

Role of TLRs in HIV-1 Infection and Potential of TLR Agonists in HIV-1 Vaccine Development and Treatment Strategies

Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors

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