ArticlePLoS pathogens2014
The epithelial αvβ3-integrin boosts the MYD88-dependent TLR2 signaling in response to viral and bacterial components.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
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- Immunoinformatics-driven design of a multi-epitope vaccine targeting neonatal rotavirus with focus on outer capsid proteins VP4 and VP7 and non structural proteins NSP2 and NSP5.Scientific reports · 2025Article
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- An updated review of HSV-1 infection-associated diseases and treatment, vaccine development, and vector therapy application.Virulence · 2024Review
- CD47 and thrombospondin-1 contribute to immune evasion byProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Integrin αvβ3 Limits Cytokine Production by Plasmacytoid Dendritic Cells and Restricts TLR-Driven Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Toll-like receptors and integrins crosstalk.Frontiers in immunology · 2024Review
- Conserved Domains in Variable Surface Lipoproteins A-G ofVeterinary sciences · 2023Article
- αVβ3 Integrin Expression Is Essential for Replication of Mosquito and Tick-Borne Flaviviruses in Murine Fibroblast Cells.Viruses · 2021Article
- ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review.International journal of molecular sciences · 2021Review
- Toll-like Receptors in Viral Encephalitis.Viruses · 2021Review
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- Phosphatases in toll-like receptors signaling: the unfairly-forgotten.Cell communication and signaling : CCS · 2021Review
- Paracoccidioides brasiliensis downmodulates α3 integrin levels in human lung epithelial cells in a TLR2-dependent manner.Scientific reports · 2020Article
- Molecular regulation of TLR signaling in health and disease: mechano-regulation of macrophages and TLR signaling.Innate immunity · 2020Review
- αvβ3-integrin regulates PD-L1 expression and is involved in cancer immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Loss of transglutaminase 2 sensitizes for diet-induced obesity-related inflammation and insulin resistance due to enhanced macrophage c-Src signaling.Cell death & disease · 2019Article
- Herpes Simplex Virus Evasion of Early Host Antiviral Responses.Frontiers in cellular and infection microbiology · 2019Review
- Spotlight on… Gabriella Campadelli-Fiume.FEMS microbiology letters · 2018Article
- Toll-like receptor signaling in macrophages is regulated by extracellular substrate stiffness and Rho-associated coiled-coil kinase (ROCK1/2).International immunology · 2018Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TLR2 is a cell surface receptor which elicits an immediate response to a wide repertoire of bacteria and viruses. Its response is usually thought to be proinflammatory rather than an antiviral. In monocytic cells TLR2 cooperates with coreceptors, e.g. CD14, CD36 and αMβ2-integrin. In an earlier work we showed that αvβ3-integrin acts in concert with TLR2 to elicit an innate response to HSV, and to lipopolysaccharide. This response is characterized by production of IFN-α and -β, a specific set of cytokines, and NF-κB activation. We investigated the basis of the cooperation between αvβ3-integrin and TLR2. We report that β3-integrin participates by signaling through Y residues located in the C-tail, known to be involved in signaling activity. αvβ3-integrin boosts the MYD88-dependent TLR2 signaling and IRAK4 phosphorylation in 293T and in epithelial, keratinocytic and neuronal cell lines. The replication of ICP0minus HSV is greatly enhanced by DN versions of MYD88, of Akt - a hub of this pathway, or by β3integrin-silencing. αvβ3-integrin enables the recruitment of TLR2, MAL, MYD88 at lipid rafts, the platforms from where the signaling starts. The PAMP of the HSV-induced innate response is the gH/gL virion glycoprotein, which interacts with αvβ3-integrin and TLR2 independently one of the other, and cross-links the two receptors. Given the preferential distribution of αvβ3-integrin to epithelial cells, we propose that αvβ3-integrin serves as coreceptor of TLR2 in these cells. The results open the possibility that TLR2 makes use of coreceptors in a variety of cells to broaden its spectrum of activity and tissue specificity.
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