Clinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on an individual’s health. We used an integrated approach of transcriptional profiling and immunological analysis to compare a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune response pathways were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T cell and B cell activation pathways was differentially regulated, independent of viral load and previous DENV infection history. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals, as demonstrated by increased activation of T cell apoptosis–related pathways and FcγRIIB (Fcγ receptor IIB) signaling associated with decreased anti-DENV–specific antibody concentrations. Together, our data illustrate that symptom-free DENV infection in children is associated with increased activation of the adaptive immune compartment and proper control mechanisms, leading to elimination of viral infection without excessive immune activation, with implications for novel vaccine development strategies.

登革热病毒（DENV）感染是节肢动物传播的最普遍的病毒性疾病，其临床症状从经典的轻度登革热到严重的，威胁生命的登革热休克综合征。但是，大多数DENV感染很少或根本没有症状。无症状DENV感染的患者提供了一个独特的机会来解密宿主的免疫反应，从而导致病毒消除，而对个人的健康没有负面影响。我们使用了转录谱分析和免疫学分析的综合方法，将柬埔寨的严格无症状病毒血症人群与临床登革热患者进行了比较。无症状个体与临床登革热患者的炎症途径和先天性免疫反应途径相似，与抗原呈递以及随后的T细胞和B细胞活化途径相关的蛋白质的表达受到差异调节，与病毒载量和先前的DENV感染史无关。反馈机制控制了无症状病毒血症患者的免疫应答，这表现为T细胞凋亡相关通路的激活增加以及与抗DENV特异性抗体浓度降低相关的FcγRIIB（Fcγ受体IIB）信号传导。总之，我们的数据表明，儿童无症状的DENV感染与适应性免疫区室的激活增加和适当的控制机制有关，从而消除了没有过度免疫激活的病毒感染，这对新型疫苗开发策略产生了影响。与病毒载量和以前的DENV感染史无关。反馈机制控制了无症状病毒血症患者的免疫应答，这表现为T细胞凋亡相关通路的激活增加以及与抗DENV特异性抗体浓度降低相关的FcγRIIB（Fcγ受体IIB）信号传导。总之，我们的数据表明，儿童无症状的DENV感染与适应性免疫区室的激活增加和适当的控制机制有关，从而消除了没有过度免疫激活的病毒感染，这对新型疫苗开发策略产生了影响。与病毒载量和以前的DENV感染史无关。反馈机制控制了无症状病毒血症患者的免疫应答，这表现为T细胞凋亡相关途径的激活增加以及与抗DENV特异性抗体浓度降低相关的FcγRIIB（Fcγ受体IIB）信号传导。总之，我们的数据表明，儿童无症状的DENV感染与适应性免疫区室的激活增加和适当的控制机制有关，从而消除了没有过度免疫激活的病毒感染，这对新型疫苗开发策略产生了影响。T细胞凋亡相关通路的激活增强以及与抗DENV特异性抗体浓度降低相关的FcγRIIB（Fcγ受体IIB）信号表明。总之，我们的数据表明，儿童无症状的DENV感染与适应性免疫区室的激活增加和适当的控制机制有关，从而消除了没有过度免疫激活的病毒感染，这对新型疫苗开发策略产生了影响。T细胞凋亡相关通路的激活增强以及与抗DENV特异性抗体浓度降低相关的FcγRIIB（Fcγ受体IIB）信号表明。总之，我们的数据表明，儿童无症状的DENV感染与适应性免疫区室的激活增加和适当的控制机制有关，从而消除了没有过度免疫激活的病毒感染，这对新型疫苗开发策略产生了影响。