Protective versus pathologic pre-exposure cytokine profiles in dengue virus infection
Protective versus pathologic pre-exposure cytokine profiles in dengue virus infection
复制标题
DOI：
10.1371/journal.pntd.0006975
复制
发表时间：
2018-12-01
影响因子：
3.8
通讯作者：
Rothman, Alan L.
中科院分区：
文献类型：
--
作者：
Friberg, Heather;Beaumier, Coreen M.;Rothman, Alan L.
背景所有四种类型的登革病毒（DENV-1-4）的高流行性传播已经在全球范围内扩大，加剧了对严重登革发病率增加的担忧。虽然大多数登革病毒感染是亚临床的，但流行病学研究表明，型交叉反应免疫可影响后续感染的疾病结局。控制这些差异的临床结果的机制仍然不明确defined.Methodology/Principal findingsBlood样本收集从一个队列的学龄泰国儿童谁随后经历了亚临床DENV感染或发展登革热疾病。在感染前收集的PBMC在体外用DENV刺激，并使用多重的基于珠的阵列测量30种细胞因子的分泌。基于用于刺激的DENV的类型和临床疾病的发生，发现细胞因子产生的显著差异。IL-15和MCP-1的分泌显著高于后来发展为症状性DENV感染的受试者的PBMC。此外，IL-6由随后发生症状性感染的所有受试者的PBMC产生，而59%的受试者发生亚临床感染。IL-12，IL-2 R，MIP-1 α，RANTES，GM-CSF和TNF α的分泌显着降低PBMC从症状infection.Conclusions/SignificanceThese数据表明显着差异预先存在的免疫反应DENV与随后的感染的临床结果。在有症状感染的受试者中发现较高水平的一些细胞因子，在亚临床感染的受试者中发现较高水平的其他细胞因子，这支持了保护性和病理性免疫特征的存在。在自然DENV感染的背景下确定的临床免疫学相关性可能有助于评估对登革热疫苗的免疫应答。
BackgroundHyperendemic circulation of all four types of dengue virus (DENV-1-4) has expanded globally, fueling concern for increased incidence of severe dengue. While the majority of DENV infections are subclinical, epidemiologic studies suggest that type-cross-reactive immunity can influence disease outcome in subsequent infections. The mechanisms controlling these differential clinical outcomes remain poorly defined.Methodology/Principal findingsBlood samples were collected from a cohort of school-aged Thai children who subsequently experienced a subclinical DENV infection or developed dengue illness. PBMC collected prior to infection were stimulated in vitro with DENV and the secretion of 30 cytokines was measured using a multiplexed, bead-based array. Significant differences were found in cytokine production based on both the type of DENV used for stimulation and the occurrence of clinical illness. Secretion of IL-15 and MCP-1 was significantly higher by PBMC of subjects who later developed symptomatic DENV infection. In addition, IL-6 was produced by PBMC from all subjects who subsequently developed symptomatic infection, versus 59% of subjects who had subclinical infection. Secretion of IL-12, IL-2R, MIP-1 alpha, RANTES, GM-CSF, and TNF alpha was significantly lower by PBMC from subjects with symptomatic infection.Conclusions/SignificanceThese data demonstrate significant differences in pre-existing immune responses to DENV associated with the clinical outcome of subsequent infection. The finding of higher levels of some cytokines in subjects with symptomatic infection and higher levels of other cytokines in subjects with subclinical infection supports the existence of both protective and pathologic immune profiles. Clinical-immunological correlations identified in the context of natural DENV infection may be useful for evaluating immune responses to dengue vaccines.