Activity

Toll-like receptor 2 senses dengue virions and mediates the innate inflammatory response underlying disease pathogenesis

Activity: Talk or presentationAcademic

Izabela Rodenhuis-Zybert - Speaker

    Exacerbated inflammation can lead to vascular permeability and plasma leakage- immune-pathologies that hallmark severe dengue virus (DENV) infection. The mechanisms underlying the aggravated inflammation during the pathogenesis of DENV infection are however incompletely understood. Here, we demonstrate that TLR2, together with its co-receptors CD14 and TLR6, is an innate sensor of DENV particles and a key mediator of the infection-mediated inflammation and immunopathology. By analyzing TLR2 expression on mononuclear blood cells isolated in an acute phase from DENV-infected pediatric patients, we found that on the susceptible to DENV infection CD14++ classical monocytes, TLR2 expression correlated with severe disease development. Consistent with these findings, blocking TLR2 prior to DENV infection in vitro abrogated NF-κB activation while CD14 and TLR6 block had a moderate effect. TLR2 block prior to DENV infection of peripheral blood mononuclear cells also prevented activation of human vascular endothelium, corroborating the potential of TLR2-responses to impair vascular integrity. Paradoxically, blocking TLR2 also significantly decreased DENV-infected cell mass, suggesting that TLR2 can serve as a putative receptor for DENV. Thus, these data highlight a novel role for TLR2 in mediating viral infection and immunopathology and provide a substantial insight to the complex interaction between the virus and innate receptors. Pharmacological targeting the TLR2 axis may therefore form a strategy for mitigating the pathogenesis of severe disease.
    11-Dec-2019

    Event (Conference)

    TitleNVvI Annual Meeting 2019
    Period11/12/201912/12/2019
    Web address (URL)
    LocationNH Leeuwenhorst
    CityNoordwijkerhout
    CountryNetherlands
    Degree of recognitionNational event

    ID: 118419398