Artikel ; Online: Capsid proteins of foot-and-mouth disease virus interact with TLR2 and CD14 to induce cytokine production.
2020 Band 223, Seite(n) 10–16
Abstract: The mechanism of recognition of the foot-and-mouth disease virus (FMDV) by host innate immune cells is not well-understood. In this study, we first found that binary ethylenimine inactivated-FMDV (BEI-FMDV) with structurally intact capsid activated TLR2, ...
| Abstract | The mechanism of recognition of the foot-and-mouth disease virus (FMDV) by host innate immune cells is not well-understood. In this study, we first found that binary ethylenimine inactivated-FMDV (BEI-FMDV) with structurally intact capsid activated TLR2, but not other TLRs, and this specific activation was blocked by anti-TLR2 Abs or knockout of TLR2. BEI-FMDV activated NF-κB to induce cytokines, notably interferon-β and IL-6, in a TLR2 and MyD88-dependent manner. Coexpression of TLR6 and CD14 showed additive effects on BEI-FMDV/TLR2-mediated activation of NF-κB. Further studies demonstrated that recombinant capsid proteins rVP1 and rVP3 of FMDV but not rVP0 bound directly with CD14 and TLR2. The rVP1- and rVP3-mediated activation of TLR2 and NF-κB were enhanced by the coexpression of TLR1 or TLR6. Immunoprecipitation of either rVP1 or rVP3 with mouse macrophage cell extracts revealed that rVP1 or rVP3 associated with TLR2, CD14 and TLR6 suggesting that rVP1 and rVP3 interact with CD14, TLR2/TLR1, and TLR2/TLR6 heterodimer. Additional study confirmed that rVP1 and rVP3 interacted with the swine TLR2 signaling pathway to induce IL-6 in swine macrophages. Our results identify VP1 and VP3 of FMDV as novel TLR agonists whose recognition by CD14, TLR2/TLR1, and TLR2/TLR6 of host innate immune cells is critical for the induction of cytokine production. |
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| Mesh-Begriff(e) | Animals ; Capsid Proteins/metabolism ; Cells, Cultured ; Foot-and-Mouth Disease/immunology ; Foot-and-Mouth Disease Virus/physiology ; HEK293 Cells ; Humans ; Immunity, Innate ; Interleukin-6/metabolism ; Lipopolysaccharide Receptors/metabolism ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B/metabolism ; Signal Transduction ; Swine ; Toll-Like Receptor 2/genetics ; Toll-Like Receptor 2/metabolism |
| Chemische Substanzen | Capsid Proteins ; Interleukin-6 ; Lipopolysaccharide Receptors ; NF-kappa B ; Tlr2 protein, mouse ; Toll-Like Receptor 2 ; VP1 protein, Foot-and-mouth disease virus ; VP3 protein, Foot-and-mouth disease virus |
| Sprache | Englisch |
| Erscheinungsdatum | 2020-04-22 |
| Erscheinungsland | Netherlands |
| Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 445150-8 |
| ISSN | 1879-0542 ; 0165-2478 |
| ISSN (online) | 1879-0542 |
| ISSN | 0165-2478 |
| DOI | 10.1016/j.imlet.2020.04.008 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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