Soluble ST2 Does Not Regulate TNF-α and IL-6 Production in Dengue Virus-Infected Human Monocytes

Marisol Pérez-Acosta,Félix Giovanni Delgado,Jaime E Castellanos

doi:10.1155/2013/230273

Abstract

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-α 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-α 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-α and IL-6. Treatment with human recombinant sST2 protein decreased lipopolysaccharide-induced monocyte TNF-α 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-α and IL-6 expression in human monocytes stimulated with LPS and DENV-2.

Highlights

Dengue is the most important arboviral disease worldwide in terms of morbidity, mortality, and economic impact [1]
The Peripheral blood mononuclear cells (PBMCs) were infected for 24 hours at a multiplicity of infection (MOI) of 0.1, and infection was verified by flow cytometry
The results showed that of the subpopulations analysed, infection was observed only in CD14+ monocytes compared to CD14+ cells treated with mock inoculum (P < 0.05) (Figure 1(a))

Summary

Introduction

Dengue is the most important arboviral disease worldwide in terms of morbidity, mortality, and economic impact [1]. Increased serum levels of sST2 protein have been reported in patients with dengue [10, 11]. Treatment with recombinant sST2 protein decreases the in vitro production of proinflammatory cytokines in murine macrophages stimulated with LPS and in vivo in murine models of sepsis, arthritis, and ischemia [16,17,18,19], conditions that involve uncontrolled inflammatory reactions. The biological importance of increased serum levels of sST2 in patients with dengue remains unknown; further, the cellular source of sST2 remains undefined. The objective of this study was to evaluate the possible immunoregulatory effects of recombinant sST2 protein on the production of proinflammatory cytokines in an in vitro model of DENV-2 infection

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Discussion

Conclusion