| Summary: | <p>Both dengue NS1 antigen and serum IL-10 levels have been shown to associate with severe clinical disease in acute dengue infection and IL-10 has also been shown to suppress dengue specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production.</p> <br/> <p>Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found the serum IL-10 levels positively correlated with dengue NS1 antigen levels (Spearmans R=0.47, p<0.0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman’s R= 0.63, p=0.001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of costimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 up to 96 hours. Apoptosis of T cells was determined by annexin V expression. Monocytes co-cultured with NS1 produced high levels of IL-10with the highest levels seen at 24 hours, and then gradually declined,. Recombinant NS1 also induced annexin V expression by both CD4+ and CD8+ T cells in a dose dependent manner although a wide individual variation was seen.</p> <br/> <p>Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes and possibly inducing apoptosis of T cells.</p>
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