Although infection with the dengue virus (DENV) causes severe dengue, it causes a mild self-limiting illness in the majority of individuals. There is emerging evidence that an aberrant immune response in the initial stages of infection lead to severe disease. Many inflammatory cytokines, chemokines, and lipid mediators are significantly higher in patients with severe dengue compared to those who develop mild infection, during febrile phase of illness. Monocytes, mast cells, and many other cells of the immune system, when infected with the DENV, especially in the presence of poorly neutralizing antibodies, leads to production of pro-inflammatory cytokines and inhibition of interferon signaling pathways. In addition, production of immunosuppressive cytokines such as IL-10 further leads to inhibition of cellular antiviral responses. This dysregulated and aberrant immune response leads to reduced clearance of the virus, and severe dengue by inducing a vascular leak and excessive inflammation due to high levels of inflammatory cytokines. Individuals with comorbid illnesses could be prone to more severe dengue due to low grade endotoxemia, gut microbial dysbiosis and an altered phenotype of innate immune cells. The immunosuppressive and inflammatory lipid mediators and altered phenotype of monocytes are likely to further act on T cells and B cells leading to an impaired adaptive immune response to the virus. Therefore, in order to identify therapeutic targets for treatment of dengue, it would be important to further characterize these mechanisms in order for early intervention. In this review, we discuss the differences in the innate immune responses in those who progress to develop severe dengue, compared to those with milder disease in order to understand the mechanisms that lead to severe dengue.

尽管登革热病毒（DENV）感染会导致严重的登革热，但在大多数人中会引起轻度的自限性疾病。越来越多的证据表明，感染初期的异常免疫反应会导致严重疾病。重症登革热患者的许多炎性细胞因子，趋化因子和脂质介体要比疾病发烧阶段轻度感染的患者高得多。单核细胞，肥大细胞和免疫系统的许多其他细胞在被DENV感染时，尤其是在中和性抗体较弱的情况下，会导致促炎性细胞因子的产生和干扰素信号传导途径的抑制。另外，免疫抑制细胞因子如IL-10的产生进一步导致细胞抗病毒应答的抑制。这种失调和异常的免疫反应导致病毒清除率降低，并由于高水平的炎性细胞因子引起血管渗漏和过度炎症而导致严重的登革热。由于低度内毒素血症，肠道微生物营养不良和先天免疫细胞表型改变，患有合并症的人可能更容易出现登革热。免疫抑制和炎性脂质介质以及单核细胞表型的改变可能进一步作用于T细胞和B细胞，从而导致对该病毒的适应性免疫反应受损。因此，为了确定登革热的治疗靶标，重要的是进一步表征这些机制以进行早期干预。在这篇评论中