title: 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.
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.
authors.affiliation: Institute of Health Sciences, Laboratory of Cellular Activation, Federal University of Triângulo Mineiro, 38025-350 Uberaba, MG, Brazil.
authors.forename: Denise Maciel
authors.initials: DM
authors.lastname: Carvalho
authors.affiliation: Institute of Health Sciences, Laboratory of Cellular Activation, Federal University of Triângulo Mineiro, 38025-350 Uberaba, MG, Brazil.
authors.forename: Fernanda Gonçalves
authors.initials: FG
authors.lastname: Garcia
authors.affiliation: Institute of Health Sciences, Laboratory of Cellular Activation, Federal University of Triângulo Mineiro, 38025-350 Uberaba, MG, Brazil.
authors.forename: Ana Paula Sarreta
authors.initials: AP
authors.lastname: Terra
authors.affiliation: Institute of Health Sciences, Laboratory of Cellular Activation, Federal University of Triângulo Mineiro, 38025-350 Uberaba, MG, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Lopes Tosta
authors.affiliation: Institute of Health Sciences, Department of Infectious and Parasitic Diseases, Federal University of Triângulo Mineiro, 38025-350 Uberaba, MG, Brazil.
authors.forename: Luciana de Almeida
authors.initials: Lde A
authors.lastname: Silva
authors.affiliation: Human Immunology Research Group, Technical Health School, Federal University of Paraiba (UFPB), 58051-900 João Pessoa, PB, Brazil.
authors.forename: Lúcio Roberto
authors.initials: LR
authors.lastname: Castellano
authors.affiliation: Institute of Health Sciences, Laboratory of Cellular Activation, Federal University of Triângulo Mineiro, 38025-350 Uberaba, MG, Brazil.
authors.forename: David Nascimento
authors.initials: DN
authors.lastname: Silva Teixeira