Abstract
BackgroundElevated IL-10 has been shown to be associated with severe dengue infection (DI). We proceeded to investigate the role of IL-10 in the pathogenesis of acute DI.Materials and methods Ex vivo and cultured IFNγ ELISpot assays for dengue virus (DENV) NS3 protein and non dengue viral proteins were carried out in 26 patients with acute DI (16 with dengue haemorrhagic fever) and 12 healthy dengue seropositive individuals from Sri Lanka. DENV serotype specific (SS) responses were determined by using a panel of SS peptides.ResultsSerum IL-10 level were significantly higher (p = 0.02) in those who did not have in vitro responses to DENV-SS peptides (mean 144.2 pg/ml) when compared to those who responded (mean 75.7 pg/ml). DENV-NS3 specific ex vivo IFNγ ELISpot responses were also significantly lower (p = 0.0001) in those who did not respond to DENV-SS peptides (mean 42 SFU/million PBMCs) when compared to those who responded to DENV-SS peptides (mean 1024 SFU/million PBMCs). Serum IL-10 levels correlated significantly (p = 0.03) and inversely (Spearmans R = −0.45) with ex vivo DENV-NS3 specific responses but not with ex vivo non DENV specific responses (Spearmans R = −014, p = 0.52). Blockage of IL-10 in vitro significantly increased (p = 0.04) the ex vivo IFNγ ELISpot DENV-NS3 specific responses but had no effect on responses to non DENV proteins.ConclusionIL-10 appears to contribute to the pathogenesis of acute dengue infections by inhibiting DENV-specific T cell responses, which can be restored by blocking IL-10.
Highlights
Dengue viral infections have become one of the most important mosquito borne viral infections in the world and are one of the major emerging infectious diseases
dengue virus (DENV)-NS3 specific ex vivo IFNc ELISpot responses were significantly lower (p = 0.0001) in those who did not respond to DENV-serotype specific (SS) peptides when compared to those who responded to DENV-SS peptides
IL-10 appears to contribute to the pathogenesis of acute dengue infections by inhibiting DENV-specific T cell responses, which can be restored by blocking IL-10
Summary
Dengue viral infections have become one of the most important mosquito borne viral infections in the world and are one of the major emerging infectious diseases. Initial infection with a particular serotype is known as a primary infection, which is usually asymptomatic or results in mild disease manifestations [5]. Severe clinical disease manifestations such as DHF/DSS are thought to result from a complex interplay between the virus, host genetic background and host immune factors. Many questions regarding factors that lead to severe disease and the pathophysiology of dengue viral infection itself remain unanswered. Both cross reactive antibodies and T cells to the previous infecting DENV serotype are thought to contribute to disease pathogenesis [5,6]. We proceeded to investigate the role of IL-10 in the pathogenesis of acute DI
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