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Both dengue NS1 antigen and serum interleukin (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. Serum IL-10 and dengue NS1 antigen levels were assessed
serially in 36 adult Sri Lankan individuals with acute dengue infection. We
found that the serum IL-10 levels correlated positively with dengue NS1
antigen levels (Spearman’s r 5 047, P < 00001), and NS1 also correlated
with annexin V expression by T cells in acute dengue (Spearman’s r 5 063,
P 5 0001). However, NS1 levels did not associate with the functionality of
T cell responses or with expression of co-stimulatory 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 for up to 96 h. Monocytes cocultured with NS1 produced high levels of IL-10, with the highest levels seen
at 24 h, and then declined gradually. Therefore, our data show that dengue
NS1 appears to contribute to pathogenesis of dengue infection by inducing
IL-10 production by monocytes.
