|
|
登革热是流行最广泛的虫媒传播的疾病，每年大约可引起5000万人的感染，12500人死亡。登革病毒属于黄病毒属，包含四种血清型，每种均可引起登革热，偶尔会引起致死性疾病。尽管对于登革病毒的病理学研究已经超过50年，然而对于该病毒如何引起严重临床疾病的机理还不是很清楚。值得一提的是，很大一部分的登革感染者并不表现临床症状（subclinical or asymptomatic）,因此这些感染病例为研究人体究竟是如何有效控制病毒提供了极佳的素材。
本文的研究者对柬埔寨的两组登革病毒感染人群进行的转录谱和免疫学分析，这两组人群分别是9名病毒感染无症状感染者和76名有症状感染者。基因表达的聚类分析显示，两组人群组内基因表达谱无明显差别，组间差别较大(图2.A)，接着通过GO分析发现这些差异表达的基因主要参与免疫应答和免疫激活(图2.B)。最后使用IPA通路富集分析发现免疫过程在无症状感染者体内激活特别明显(图2.C)。
图2
进一步对IPA得到的结果进行细致分析，发现无症状组和有症状组在先天性免疫反应激活方面没有显著差异。相应地，先天性免疫细胞产生的细胞因子浓度(如IL-8，IL-15，CCL3等)无明显差别(图3)。
图三
在无症状人群中激活最明显的通路是活化T细胞核因子(NFAT) 通路(图2.C).NFAT是适应性免疫应答的主要调节因子，在免疫细胞被抗原激活后表达。作者从相应的细胞因子上进行了验证(图四. B 和C)。上述结果显示无症状组和有症状组的主要差别在适应性免疫方面。
图四
最后作者发现和有症状组相比，无症状组的T细胞活化和凋亡程度更高，相反地，无症状组B细胞浆化程度更低，产生的抗体浓度更低。作者推测这种对免疫反应的适当反馈调节有助于感染者控制体内病毒,低亲和力、异质性的抗体反而会促进登革病毒感染抗原呈递细胞。
本研究揭示了T细胞在机体控制登革病毒中的作用，或将对以后的疫苗研发提供思路。
文献信息：
Title:Increased adaptive immune responses and proper feedback regulation protect against clinical dengue
Abstract: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. |
|
发表于 2017-9-10 11:04:10
发表于 2017-9-10 12:50:13
发表于 2017-9-11 14:50:35
