Abstract

Changes in immune response during lifespan of man are well known. These changes involve decreased neonatal and elderly immune response. In addition, it has been shown a relationship between immune and oxidative mechanisms, suggesting that altered immune response could be associated to altered oxidative response. Increased expression of nitric oxide (NO) has been documented in dengue and in monocyte cultures infected with different types of dengue virus. However, there is no information about the age-dependent NO oxidative response in humans infected by dengue virus. In this study, monocyte cultures from neonatal, elderly and adult individuals (n = 10 each group) were infected with different dengue virus types (DENV- 1 to 4) and oxidative/antioxidative responses and apoptosis were measured at days 1 and 3 of culture. Increased production of NO, lipid peroxidation and enzymatic and nonenzymatic anti-oxidative responses in dengue infected monocyte cultures were observed. However, neonatal and elderly monocytes had lower values of studied parameters when compared to those in adult-derived cultures. Apoptosis was present in infected monocytes with higher values at day 3 of culture. This reduced oxidant/antioxidant response of neonatal and elderly monocytes could be relevant in the pathogenesis of dengue disease.

Highlights

  • Monocytes/macrophages (Mo/MW) represent one of the important targets during dengue infection and are important in viral dissemination [1,2,3]

  • Lower values in nitric oxide (NO) and MDA productions (Figures 1 and 2; Tables S1 and S2), catalase and Superoxide dismutase (SOD) activities (Figures 3 and 4; Tables S3 and S4) and GSH content (Figure 5; Table S5) were found in neonatal-monocytes, following by elderly-monocytes and the highest values were observed in adult-monocytes (Figure 6); except increased activity of SOD observed in elderly monocytes (Figure 6D)

  • These findings were observed at days 1 and 3 post-infection and the pattern of monocyte response induced by dengue virus was similar to that observed in LPS-treated cultures

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Summary

Introduction

Monocytes/macrophages (Mo/MW) represent one of the important targets during dengue infection and are important in viral dissemination [1,2,3]. It has been reported that the immune alterations can influence oxidative metabolism and vice versa [7] In this regard, monocytes from neonates and elderly individuals have been shown to have immunosuppressive status against infections [8,9,10,11,12,13,14,15], suggesting a possible altered oxidative response. The aim of this study was to analyze the oxidant (nitric oxide) and antioxidant (catalase, superoxide dismutase and reduced glutathione) responses of monocyte from neonates, young adults and elderly subjects during an in vitro dengue virus infection. During this study both elderly and neonatal monocytes had lower oxidant/antioxidant responses to dengue virus infection. These findings are probably important in the pathogenesis of dengue disease in individuals from those age groups

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