Suppression of Virus Specific Immune Responses by IL-10 in Acute Dengue Infection
Suppression of Virus Specific Immune Responses by IL-10 in Acute Dengue Infection
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DOI：
10.1371/journal.pntd.0002409
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发表时间：
2013-09-01
影响因子：
3.8
通讯作者：
Ogg, Graham Stuart
中科院分区：
文献类型：
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作者：
Malavige, Gathsaurie Neelika;Jeewandara, Chandima;Ogg, Graham Stuart
背景：IL-10升高已被证明与严重登革热感染（DI）相关。我们着手调查IL-10在急性DI的发病机制中的作用。材料和方法：离体和培养的IFN γ ELISpot检测登革病毒（DENV）NS 3蛋白和非登革病毒蛋白进行了26例急性DI（16与登革出血热）和12个健康的登革热血清阳性个体从斯里兰卡。结果：与有应答者（平均75.7pg/ml）相比，对DENV-SS肽无体外应答者（平均144.2pg/ml）血清IL-10水平显著升高（p = 0.02）。与对DENV-SS肽有应答的那些（平均1024 SFU/百万PBMC）相比，在对DENV-SS肽无应答的那些（平均42 SFU/百万PBMC）中，DENV-NS 3特异性离体IFN γ ELISpot应答也显著较低（p = 0.0001）。血清IL-10水平与离体DENV-NS 3特异性应答显著（p = 0.03）和负相关（Spearmans R = 20.45），但与离体非DENV特异性应答不相关（Spearmans R =-014，p = 0.52）。IL-10在体外阻断显着增加（p = 0.04）的离体IFN γ ELISpot DENV-NS 3特异性反应，但对非DENV蛋白的反应没有影响。结论：IL-10似乎有助于急性登革感染的发病机制，通过抑制DENV特异性T细胞反应，这可以通过阻断IL-10恢复。
Background: Elevated 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 IFN gamma 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.Results: Serum 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 IFN gamma 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 = 20.45) 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 IFN gamma ELISpot DENV-NS3 specific responses but had no effect on responses to non DENV proteins.Conclusion: 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.