Dengue virus (DENV) produces an acute infection that results in the overproduction of proinflammatory cytokines. Although increased levels of the immunoregulator soluble ST2 (sST2) protein have been reported in the serum of patients with dengue, its importance during DENV infection remains unclear. The purpose of this study was to evaluate the effect of a recombinant human sST2 protein on the production of TNF- and IL-6 in an in vitro model of DENV infection. Peripheral blood mononuclear cells (PBMCs) were permissive to in vitro DENV infection since viral antigen was detected in CD14+ monocytes by flow cytometry (median, 1%; range, 0–2.2), and in their supernatants TNF- and IL-6 were detected. However, sST2 protein was not detected. Using multiple staining on infected PBMC we found that only CD14+ cells produced TNF- and IL-6. Treatment with human recombinant sST2 protein decreased lipopolysaccharide-induced monocyte TNF- and IL-6 production. However, this effect was not observed when the monocytes were pretreated with sST2 and later infected with DENV-2. These results suggest that sST2 has different roles in the regulation of TNF- and IL-6 expression in human monocytes stimulated with LPS and DENV-2. 1. Introduction Currently, dengue is the most important arboviral disease worldwide in terms of morbidity, mortality, and economic impact [1]. Peripheral blood mononuclear cells (PBMCs) are cellular targets for dengue virus (DENV) infection [2], with monocytes being preferentially infected [3, 4]. However, data exist suggesting that T and B lymphocytes can also become infected [5, 6]. Following dengue infection, the virus induces production and liberation of proinflammatory cytokines such as TNF-α and IL-6, which induce changes in vascular permeability, a dominant clinical trait of severe dengue infections [5, 7–9]. Increased serum levels of sST2 protein have been reported in patients with dengue [10, 11]. The interleukin-1 receptor-like-1 protein (IL1RL1), also known as ST2, is a member of the IL1R/Toll-like receptor (TLR) superfamily [12]. The ST2 gene has three isoforms generated from alternative mRNA splicing: a membrane-anchored long form (ST2L), a secreted soluble form (sST2), and a membrane-anchored variant form (ST2V) [13, 14]. It has been postulated that both ST2L and sST2 are involved in the control of cytokine expression during inflammatory events to regulate exacerbated inflammatory responses [15]. Treatment with recombinant sST2 protein decreases the in vitro production of proinflammatory cytokines in murine macrophages stimulated with LPS and
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