Abstract
Mast cells (MCs), a type of immune effector cell, have recently become recognized for their ability to cause vascular leakage during dengue virus (DENV) infection. Although MC stabilizers have been reported to attenuate DENV induced infection in animal studies, there are limited in vitro studies on the use of MC stabilizers against DENV induced MC degranulation. 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA) has been reported to be a potential MC stabilizer by inhibiting IgE-mediated MC activation in both cellular and animal models. The present study aims to establish an in vitro model of DENV3-induced RBL-2H3 cells using ketotifen fumarate as a control drug, as well as to determine the effect of tHGA on the release of MC mediators upon DENV infection. Our results demonstrated that the optimal multiplicities of infection (MOI) were 0.4 × 10−2 and 0.8 × 10−2 focus forming units (FFU)/cell. Ketotifen fumarate was proven to attenuate DENV3-induced RBL-2H3 cells degranulation in this in vitro model. In contrast, tHGA was unable to attenuate the release of both β-hexosaminidase and tumor necrosis factor (TNF)-α. Nonetheless, our study has successfully established an in vitro model of DENV3-induced RBL-2H3 cells, which might be useful for the screening of potential MC stabilizers for anti-dengue therapies.
Highlights
Dengue virus (DENV) infection is an increasing problem in both tropical and subtropical areas and remains endemic in more than 100 countries worldwide
For better comparison with earlier studies where rat basophilic leukemic (RBL)-2H3 cells were infected by DENV3, the present study measured the degree of degranulation by examining the release of β-hexosaminidase in order to determine the optimal multiplicities of infection (MOI) to be used
These findings indicated that the optimal MOI of clinically isolated DENV3 for the screening of mast cell (MC) stabilizers in DENV infection ranges between 0.4 × 10−2 and 0.8 × 10−2 focus forming units (FFU)/cell
Summary
Dengue virus (DENV) infection is an increasing problem in both tropical and subtropical areas and remains endemic in more than 100 countries worldwide. DENV is an arthropod-borne single stranded RNA virus of the Flavivirus genus. It is comprised of four distinct serotypes – DENV-1, -2, -3, and -4 – with 65–70% sequence homology and all serotypes contribute to dengue infection in humans [3,4]. DENV infection will result in dengue fever (DF), which is a self-resolving febrile disease. DengvaxiaTM, the first approved dengue vaccine, has been used in a few countries but since 2017, its usage in Philippines has been suspended. This is because of its unequal protection against the four different serotypes of the License 4.0 (CC BY)
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