SARS‐CoV‐2 infection activates dendritic cells via cytosolic receptors rather than extracellular TLRs

Donk, Lieve E. H. van der; Eder, Julia; Hamme, John L. van; Brouwer, Philip J.M.; Brinkkemper, Mitch; Nuenen, Ad C. van; Gils, Marit J. van; Sanders, Rogier W.; Kootstra, Neeltje A.; Bermejo‐Jambrina, Marta; Geijtenbeek, Teunis B. H.

doi:10.1002/eji.202149656

Cited by 12 publications

(25 citation statements)

References 42 publications

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“…Intracellular viral sensors play master roles in identifying SARS-CoV-2, leading to effective type I IFNs and cytokine responses. Moreover, it is possible for SARS-CoV-2 to escape TLR perception, which may account that, the body has not yet established effective immunity against the virus at the initial stage of SARS-CoV-2 invasion ( van der Donk et al, 2022 ). This leads to inefficient DCs activation and subsequent abnormal inflammatory responses.…”

Section: Tlrs Sensing Of Sars-cov-2mentioning

confidence: 99%

Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

Liu

Yang

et al. 2022

Front. Pharmacol.

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Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) rapidly infects humans and animals which make coronavirus disease 2019 (COVID-19) a grievous epidemic worldwide which broke out in 2020. According to data analysis of the other coronavirus family, for instance severe acute respiratory syndrome SARS coronavirus (SARS-CoV), can provide experience for the mutation of SARS-CoV-2 and the prevention and treatment of COVID-19. Toll-like receptors (TLRs) as a pattern recognition receptor (PRRs), have an indispensable function in identifying the invader even activate the innate immune system. It is possible for organism to activate different TLR pathways which leads to secretion of proinflammatory cytokines such as Interleukin 1 (IL-1), Interleukin 6 (IL-6), Tumor necrosis factor α (TNFα) and type Ⅰ interferon. As a component of non-specific immunity, TLRs pathway may participate in the SARS-CoV-2 pathogenic processes, due to previous works have proved that TLRs are involved in the invasion and infection of SARS-CoV and MERS to varying degrees. Different TLR, such as TLR2, TLR4, TLR7, TLR8 and TLR9 probably have a double-sided in COVID-19 infection. Therefore, it is of great significance for a correctly acknowledging how TLR take part in the SARS-CoV-2 pathogenic processes, which will be the development of treatment and prevention strategies.

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Section: Tlrs Sensing Of Sars-cov-2mentioning

confidence: 99%

Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

Liu

Yang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

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“…It is also important to take into account that SARS-CoV-2 seems to escape direct recognition by TLR4, as shown by van der Donk et al [ 102 ], which could explain the inefficient immunity to SARS-CoV-2 during the early stages of infection. Indeed, plasmocytoid dendritic cells (pDCs) seem to sense SARS-CoV-2 via the following two distinct innate immune pathways: the endosomal TLR7 pathway activated through viral RNA, which leads to type I IFN production, and the TLR2 pathway triggered by the recognition of the viral envelope protein, inducing IL-6 production [ 103 ].…”

Section: Immunosuppressionmentioning

confidence: 99%

Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?

et al. 2023

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The relationship between viral infections and the risk of developing cancer is well known. Multiple mechanisms participate in and determine this process. The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in the deaths of millions of people worldwide. Although the effects of COVID-19 are limited for most people, a large number of people continue to show symptoms for a long period of time (long COVID). Several studies have suggested that cancer could also be a potential long-term complication of the virus; however, the causes of this risk are not yet well understood. In this review, we investigated arguments that could support or reject this possibility.

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“…Still, others also report a lack of authentic activation in their model systems. For instance, monocyte-derived dendritic cells, which abundantly express TLR4 and other TLRs, were not activated by authentic SARS-CoV-2 particles, S pseudoparticles or recombinant S protein ( van der Donk et al, 2022 ). While the evidence points towards S1 or S2 as the trigger for a proinflammatory response, and TLR4 or TLR2 as the primary mediator of this response ( Khan et al, 2021 ; Shirato and Kizaki, 2021 ; Zhao et al, 2021 ; Frank et al, 2022 ), another study suggested a role for the SARS-CoV-2 E protein in the production of inflammatory cytokines ( Zheng et al, 2021 ).…”

Section: The Role Of Tlr4 and Spike In The Proinflammatory Response T...mentioning

confidence: 99%

Activation of TLR4 by viral glycoproteins: A double-edged sword?

et al. 2022

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Recognition of viral infection by pattern recognition receptors is paramount for a successful immune response to viral infection. However, an unbalanced proinflammatory response can be detrimental to the host. Recently, multiple studies have identified that the SARS-CoV-2 spike protein activates Toll-like receptor 4 (TLR4), resulting in the induction of proinflammatory cytokine expression. Activation of TLR4 by viral glycoproteins has also been observed in the context of other viral infection models, including respiratory syncytial virus (RSV), dengue virus (DENV) and Ebola virus (EBOV). However, the mechanisms involved in virus-TLR4 interactions have remained unclear. Here, we review viral glycoproteins that act as pathogen-associated molecular patterns to induce an immune response via TLR4. We explore the current understanding of the mechanisms underlying how viral glycoproteins are recognized by TLR4 and discuss the contribution of TLR4 activation to viral pathogenesis. We identify contentious findings and research gaps that highlight the importance of understanding viral glycoprotein-mediated TLR4 activation for potential therapeutic approaches.

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SARS‐CoV‐2 infection activates dendritic cells via cytosolic receptors rather than extracellular TLRs

Cited by 12 publications

References 42 publications

Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?

Activation of TLR4 by viral glycoproteins: A double-edged sword?

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