BACKGROUND: Dengue fever (DF) is the most rapidly spreading mosquito-borne viral disease. Practical vaccines or specific therapeutics are still expected. Environmental factors and genetic factors affect the susceptibility of Dengue virus (DV) infection. Asthma is a common allergic disease, with house dust mites (HDMs) being the most important allergens. Asthmatic patients are susceptible to several microorganism infections. METHODS: A nationwide population-based cohort analysis was designed to assess whether to determine whether asthma can be a risk factor for DF. RESULTS: Unexpectedly, our data from a nationwide population-based cohort revealed asthmatic patients are at a decreased risk of DF. Compared to patients without asthma, the hazard ratio (HR) for DF in patients with asthma was 0.166 (95% CI: 0.118-0.233) after adjustment for possible confounding factors. In the age stratification, the adjusted HR for DF in young adult patients with asthma was 0.063. Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) of dendritic cells (DCs) is an important entry for DV. Through another in vitro experiment, we found that HDM can diminish surface expression of DC-SIGN in monocyte-derived DCs and further decrease the cellular entry of DV. CONCLUSIONS: Decreased DC-SIGN expression in DCs of allergic asthmatic patient may be one of many factors for them to be protected against DF. This could implicate the potential for DC-SIGN modulation as a candidate target for designing therapeutic strategies for DF.