title: Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.
abstract: 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 = 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 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 co-cultured 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.
authors.affiliation: Centre for Dengue Research, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.
authors.forename: T N
authors.initials: TN
authors.lastname: Adikari
authors.affiliation: Centre for Dengue Research, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.
authors.forename: L
authors.initials: L
authors.lastname: Gomes
authors.affiliation: Centre for Dengue Research, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.
authors.forename: N
authors.initials: N
authors.lastname: Wickramasinghe
authors.affiliation: Radcliffe Department of Medicine, MRC Human Immunology Unit, NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Salimi
authors.affiliation: Centre for Dengue Research, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.
authors.forename: N
authors.initials: N
authors.lastname: Wijesiriwardana
authors.affiliation: Centre for Dengue Research, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.
authors.forename: A
authors.initials: A
authors.lastname: Kamaladasa
authors.affiliation: Department of Medicine, Faculty of Medical Sciences, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.
authors.forename: N L A
authors.initials: NL
authors.lastname: Shyamali
authors.affiliation: Radcliffe Department of Medicine, MRC Human Immunology Unit, NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, Oxford, UK.
authors.forename: G S
authors.initials: GS
authors.lastname: Ogg
authors.affiliation: Centre for Dengue Research, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.|Radcliffe Department of Medicine, MRC Human Immunology Unit, NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, Oxford, UK.
authors.forename: G N
authors.initials: GN
authors.lastname: Malavige
mesh_terms: D000208:Acute Disease; D000328:Adult; D017304:Annexin A5 / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D003715:Dengue / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003716:Dengue Virus / Q000276:immunology / Q000472:pathogenicity; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D061251:Primary Cell Culture; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; C508609:IL10 protein, human; C082515:NS1 protein, dengue-1 virus; D017361:Viral Nonstructural Proteins; D016753:Interleukin-10
keywords: IL-10; NS1 antigen; T cell function; dengue infection; monocytes