Elevated dengue virus nonstructural protein 1 serum levels and altered toll-like receptor 4 expression, nitric oxide, and tumor necrosis factor alpha production in dengue hemorrhagic Fever patients.

Denise Maciel Carvalho,David Nascimento Silva Teixeira,Lúcio Roberto Castellano,Fernanda Gonçalves Garcia,Luciana De Almeida Silva,Ana Paula Sarreta Terra,Ana Cristina Lopes Tosta

doi:10.1155/2014/901276

Denise Maciel Carvalho, David Nascimento Silva Teixeira + Show 5 more

Open Access

https://doi.org/10.1155/2014/901276

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Abstract

Background. During dengue virus (DV) infection, monocytes produce tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1) on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1) serum levels and innate immune response (TLR4 expression and TNF-α/NO production) of DV infected patients presenting different clinical outcomes. Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA), TNF-α production by peripheral blood mononuclear cells (PBMCs), and TLR4 expression on CD14+ cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF) was detected compared to patients with dengue hemorrhagic fever (DHF). Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-α production) when compared to DF patients. Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes.

Highlights

Dengue virus (DV) infects 50–100 million people worldwide every year and an additional 2.5 billion people are at high risk, living in dengue endemic areas [1,2,3]
peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood samples of healthy controls (HCs) and dengue virus (DV) infected patients by density gradient centrifugation using Ficoll-Hypaque
The PBMCs were stimulated for 24 h in the presence or absence of a toll-like receptor 4 (TLR4) agonist 10 μg/mL of ultrapure lipopolysaccharide (LPS; InVivoGen, USA)

Summary

Introduction

Dengue virus (DV) infects 50–100 million people worldwide every year and an additional 2.5 billion people are at high risk, living in dengue endemic areas [1,2,3]. DVs were susceptible to a NO donor treatment and viruses were detected at higher rates in infected cells after iNOS inhibition, indicating that NO might play an important role in controlling monocytes DV infection [21] It seems that TNF-α and NO would be involved in generating severe symptoms [22, 23] and in the elimination of viruses [24,25,26]. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1) serum levels and innate immune response (TLR4 expression and TNF-α/NO production) of DV infected patients presenting different clinical outcomes. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes

Objectives

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