Green Sharone, Rothman Alan
University of Massachusetts Medical School, Center for Infectious Disease and Vaccine Research, Worcester, Massachusetts 01655, USA.
Curr Opin Infect Dis. 2006 Oct;19(5):429-36. doi: 10.1097/01.qco.0000244047.31135.fa.
The continued emergence of dengue virus infection and its severe disease manifestation, dengue hemorrhagic fever, is a growing public health problem. The majority of severe infections occur upon secondary encounters with heterologous dengue virus serotypes, suggesting an immune-mediated process.
Significant findings in the past year include a greater understanding of dengue virus interactions with target cells such as dendritic cells, hepatocytes and endothelial cells. Infection of these cells results in the production of immune mediators that then shape the adaptive humoral and cellular immune response. The circulation of high levels of secreted NS1 in the presence of pre-existing heterologous non-neutralizing antibody may mediate complement activation and trigger plasma leakage. The role of enhancing antibodies in disease pathogenesis remains unclear. Recent studies demonstrate low avidity crossreactive T cells, which may produce an altered profile of cytokines leading to plasma leakage. Ongoing prospective studies that include epidemiological, virological and immunological risk factors are crucial to our understanding of the mechanisms of immunopathogenesis of dengue hemorrhagic fever.
The immune mechanisms that lead to dengue hemorrhagic fever are complex and need to be elucidated further for the development of therapeutics as well as safe and efficacious dengue vaccines.
登革病毒感染及其严重疾病表现——登革出血热持续出现，这是一个日益严重的公共卫生问题。大多数严重感染发生在再次接触异源登革病毒血清型时，提示这是一个免疫介导的过程。
过去一年的重要发现包括对登革病毒与靶细胞（如树突状细胞、肝细胞和内皮细胞）相互作用有了更深入的了解。这些细胞被感染会导致免疫介质的产生，进而塑造适应性体液免疫和细胞免疫反应。在预先存在异源非中和抗体的情况下，高水平分泌型NS1的循环可能介导补体激活并引发血浆渗漏。增强性抗体在疾病发病机制中的作用仍不清楚。最近的研究表明存在低亲和力交叉反应性T细胞，这可能会产生改变的细胞因子谱，导致血浆渗漏。正在进行的包括流行病学、病毒学和免疫学危险因素的前瞻性研究对于我们理解登革出血热免疫发病机制至关重要。
导致登革出血热的免疫机制很复杂，为了开发治疗方法以及安全有效的登革疫苗，需要进一步阐明。
