SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion

Gardiman, Elisa; Bianchetto-Aguilera, Francisco M.; Gasperini, Sara; Tiberio, Laura; Scandola, Matteo; Lotti, Virginia; Gibellini, Davide; Salvi, Valentina; Bosisio, Daniela; Cassatella, Marco Antonio; Tamassia, Nicola

doi:10.3390/cells11233785

Cited by 12 publications

(11 citation statements)

References 59 publications

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“…However, in the HEK293 NF-κB luciferase reporter assays, the activation of hTLR7 by SAMPs is far less significant than that of hTLR8. In neutrophiles, the activation of hTLR8 but not hTLR7 is observed 52 . Further, in an acute graft-versus-host disease study, serum miR-29a has been shown to be able to activate mTlr7 in mouse DCs and hTLR8 in human DCs 44 .…”

Section: Discussionmentioning

confidence: 98%

MiR-574-5p activates human TLR8 to promote autoimmune signaling and lupus

Wang,

Song,

et al. 2023

Preprint

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Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis.

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Section: Discussionmentioning

confidence: 98%

MiR-574-5p activates human TLR8 to promote autoimmune signaling and lupus

Wang,

Song,

et al. 2023

Preprint

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“…At least partially, this activation of PMNs could be directly determined by the virus. It was recently described by [45], that single-strand RNAs from the SARS-CoV-2 genome is able to activate human neutrophils via TLR8, triggering a remarkable production of TNFα, IL-1ra, and CXCL8, apoptosis delay, modulation of CD11b and CD62L expression, and release of neutrophil extracellular traps. This exuberant contribution of PMNs to the interstitial pneumonia that occurs in COVID-19 was, in many aspects, reproduced in hACE2 mouse model infected with SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Experimental Lung Inflammation Induced by Inactivated SARS-CoV-2 is Controlled by Intranasal Instillation of Vitamin D

Souza¹,

Zorzella-Pezavento²,

Ayupe³

et al. 2023

Preprint

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COVID-19 is a pandemic triggered by the coronavirus SARS-CoV-2 whose peak occurred in the years 2020 and 2021. The main target of the virus is the lung and infection is associated to an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 mice and then the evaluation of vitamin D (VitD) ability to control this process. The assays used to estimate the severity of lung involvement included total and differential number of cells in the BALF, histopathological analysis, quantification of T cell subsets and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates and flow cytometric analysis of cells recovered from lung parenchyma. IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in COVID-19 patients. This inflammatory process was significantly decreased by IN delivery of vitD, but not by its IP administration, suggesting that this hormone has therapeutic potential in COVID-19 if locally applied.

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“…This activation of PMNs could be directly determined by the virus. It was recently described [ 53 ] that single-strand RNAs from the SARS-CoV-2 genome are able to activate human neutrophils via TLR8, triggering a remarkable production of TNF-α, IL-1ra, and CXCL8, apoptosis delay, the modulation of CD11b and CD62L expression, and the release of NETs. Additionally, the tissue damage induced by the neutrophilic infiltration can activate the inflammasome, as described above, resulting in more inflammation and neutrophil recruitment, perpetuating, therefore, the inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D

Souza

Zorzella-Pezavento

Ayupe

et al. 2023

Cells

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The COVID-19 pandemic was triggered by the coronavirus SARS-CoV-2, whose peak occurred in the years 2020 and 2021. The main target of this virus is the lung, and the infection is associated with an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 female mice, and then the evaluation of the ability of vitamin D (VitD) to control this process. The assays used to estimate the severity of lung involvement included the total and differential number of cells in the bronchoalveolar lavage fluid (BALF), histopathological analysis, quantification of T cell subsets, and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates, and flow cytometric analysis of cells recovered from lung parenchyma. The IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in transgenic mice infected with SARS-CoV-2. This inflammatory process was significantly decreased by the IN delivery of VitD, but not by its IP administration, suggesting that this hormone could have a therapeutic potential in COVID-19 if locally applied. To our knowledge, the local delivery of VitD to downmodulate lung inflammation in COVID-19 is an original proposition.

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SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion

Cited by 12 publications

References 59 publications

MiR-574-5p activates human TLR8 to promote autoimmune signaling and lupus

MiR-574-5p activates human TLR8 to promote autoimmune signaling and lupus

Experimental Lung Inflammation Induced by Inactivated SARS-CoV-2 is Controlled by Intranasal Instillation of Vitamin D

Lung Inflammation Induced by Inactivated SARS-CoV-2 in C57BL/6 Female Mice Is Controlled by Intranasal Instillation of Vitamin D

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