Differential roles of RIG-I-like receptors in SARS-CoV-2 infection

Yang, Duomeng; Geng, Tingting; Harrison, Andrew G.; Wang, Penghua

doi:10.1101/2021.02.10.430677

Cited by 16 publications

(15 citation statements)

References 22 publications

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“…The induction of cytokine production in MNPs in COVID-19 can either be triggered via recognition of damage-associated molecular patterns (DAMPS) released from epithelial cells affected by SARS-CoV-2 by PRRs or by direct recognition of viral pathogen-associated molecular patterns (PAMPs) via specific Toll-like receptors, i.e. TLR2 and TLR4, the retinoic acid-inducible gene I (RIG-I) or the melanoma differentiation associated gene (MDA)-5 (116)(117)(118)(119). Furthermore, C-type lectin receptors, including DC-SIGN, L-SIGN, LSECtin, ASGR1, CLEC4K (Langerin) and CLEC10A (MGL), as well as Tweety family member 2 have been identified to interact with the SARS-CoV-2 spike protein inducing proinflammatory responses, but not allowing direct infection.…”

Section: The Role Of Monocytes and Alveolar Macrophages In Covid-19mentioning

confidence: 99%

Monocytes and Macrophages in COVID-19

2021

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COVID-19 is a contagious viral disease caused by SARS-CoV-2 that led to an ongoing pandemic with massive global health and socioeconomic consequences. The disease is characterized primarily, but not exclusively, by respiratory clinical manifestations ranging from mild common cold symptoms, including cough and fever, to severe respiratory distress and multi-organ failure. Macrophages, a heterogeneous group of yolk-sac derived, tissue-resident mononuclear phagocytes of complex ontogeny present in all mammalian organs, play critical roles in developmental, homeostatic and host defense processes with tissue-dependent plasticity. In case of infection, they are responsible for early pathogen recognition, initiation and resolution of inflammation, as well as repair of tissue damage. Monocytes, bone-marrow derived blood-resident phagocytes, are recruited under pathological conditions such as viral infections to the affected tissue to defend the organism against invading pathogens and to aid in efficient resolution of inflammation. Given their pivotal function in host defense and the potential danger posed by their dysregulated hyperinflammation, understanding monocyte and macrophage phenotypes in COVID-19 is key for tackling the disease’s pathological mechanisms. Here, we outline current knowledge on monocytes and macrophages in homeostasis and viral infections and summarize concepts and key findings on their role in COVID-19. While monocytes in the blood of patients with moderate COVID-19 present with an inflammatory, interferon-stimulated gene (ISG)-driven phenotype, cellular dysfunction epitomized by loss of HLA-DR expression and induction of S100 alarmin expression is their dominant feature in severe disease. Pulmonary macrophages in COVID-19 derived from infiltrating inflammatory monocytes are in a hyperactivated state resulting in a detrimental loop of pro-inflammatory cytokine release and recruitment of cytotoxic effector cells thereby exacerbating tissue damage at the site of infection.

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Section: The Role Of Monocytes and Alveolar Macrophages In Covid-19mentioning

confidence: 99%

Monocytes and Macrophages in COVID-19

2021

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“…Indeed, DCs are equipped with a wide arsenal of PRRs responsible for the detection of several viral components. Among the PRRs involved in SARS-CoV-2 sensing are TLR7 [59], RIG-I [60], MDA5 [61] and possibly cGAS-STING [62]. Upon binding to their agonists, PRRs initiate a signaling pathway which culminates in the activation of IRF3, IRF7 and NF-κB.…”

Section: Sars-cov-2: Mechanisms Of Recognition and Early Immune Responsementioning

confidence: 99%

How dendritic cells sense and respond to viral infections

et al. 2021

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The ability of dendritic cells (DCs) to sense viral pathogens and orchestrate a proper immune response makes them one of the key players in antiviral immunity. Different DC subsets have complementing functions during viral infections, some specialize in antigen presentation and cross-presentation and others in the production of cytokines with antiviral activity, such as type I interferons. In this review, we summarize the latest updates concerning the role of DCs in viral infections, with particular focus on the complex interplay between DC subsets and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Despite being initiated by a vast array of immune receptors, DC-mediated antiviral responses often converge towards the same endpoint, that is the production of proinflammatory cytokines and the activation of an adaptive immune response. Nonetheless, the inherent migratory properties of DCs make them a double-edged sword and often viral recognition by DCs results in further viral dissemination. Here we illustrate these various aspects of the antiviral functions of DCs and also provide a brief overview of novel antiviral vaccination strategies based on DCs targeting.

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“…Studies have shown that SARS-CoV-2 RNA could trigger activation of the RIG-I-MAVS pathway and enhance the release of type-I IFN [ 129 ]. Yang et al [ 130 ] found that after knocking out RIG-I, MDA5, or mitochondrial antiviral-signaling protein (MAVS), SARS-CoV-2-infected human endothelial cells produced notably less type-I/III IFN and the expression of ACE2 was increased. In alveolar epithelial cells, ORF9B inhibited the release of IFN, thereby inhibiting antiviral immunity [ 129 ].…”

Section: Ace2 Sars-cov-2 and Innate Immune Pathwaysmentioning

confidence: 99%

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

Chen

Yin

et al. 2021

IJMS

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Despite the protracted battle against coronavirus acute respiratory infection (COVID-19) and the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no specific and effective drugs have to date been reported. Angiotensin-converting enzyme 2 (ACE2) is a zinc metalloproteinase and a critical modulator of the renin-angiotensin system (RAS). In addition, ACE2 has anti-inflammatory and antifibrosis functions. ACE has become widely known in the past decade as it has been identified as the primary receptor for SARS-CoV and SARS-CoV-2, being closely associated with their infection. SARS-CoV-2 primarily targets the lung, which induces a cytokine storm by infecting alveolar cells, resulting in tissue damage and eventually severe acute respiratory syndrome. In the lung, innate immunity acts as a critical line of defense against pathogens, including SARS-CoV-2. This review aims to summarize the regulation of ACE2, and lung host cells resist SARS-CoV-2 invasion by activating innate immunity response. Finally, we discuss ACE2 as a therapeutic target, providing reference and enlightenment for the clinical treatment of COVID-19.

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Differential roles of RIG-I-like receptors in SARS-CoV-2 infection

Cited by 16 publications

References 22 publications

Monocytes and Macrophages in COVID-19

Monocytes and Macrophages in COVID-19

How dendritic cells sense and respond to viral infections

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

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