Dengue (DEN) represents probably the most serious arthropod-borne viral disease. leakage compared to DENV2-infected mice created to dengue na?ve mothers. With this ADE model we shown the part of TNF- in DEN-induced D-106669 vascular leakage. Furthermore, upon illness with an attenuated DENV2 mutant strain, mice created to DENV1-immune mothers developed lethal disease D-106669 accompanied by vascular leakage whereas infected mice created to dengue na?ve mothers did no display any clinical manifestation. ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice created to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice created to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct demonstration of the part of maternally acquired heterotypic dengue antibodies in the enhancement of dengue disease severity and offers a unique opportunity to further decipher the mechanisms involved. Author Summary Dengue (DEN) is an arthropod-transmitted viral disease which affects approximately 390 million individuals in the tropical and subtropical world annually. DEN medical manifestations range from mild febrile illness (dengue fever) to life-threatening dengue hemorrhagic/dengue shock syndrome (DHF/DSS). Epidemiological observations show that infants created to dengue immune mothers are at greater risk to develop the severe form of the disease (DHF/DSS) upon illness with any serotype of dengue disease (DENV). It was proposed that the presence of maternally acquired DENV specific antibodies cross react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Direct experimental evidence assisting this antibody-dependent enhancement (ADE) hypothesis has been missing. Furthermore, a recent epidemiological statement offers challenged the influence of maternally acquired antibodies in disease end result. Here, we have developed a mouse model of ADE where DENV2-infected mice created to DENV1 immune mothers displayed enhanced disease severity compared to DENV2-infected mice created to dengue na?ve mothers. This is a long-overdue direct experimental evidence of the part of maternally acquired antibodies in dengue disease end result. It provides a unique opportunity to dissect the mechanisms involved in this phenomenon. Intro Dengue (DEN) is the most common arthropod-borne viral illness in the world . Approximately 3 billion folks who are living in the tropical and subtropical areas from Southeast Asia, the Pacific and the Americas are at risk of illness C. A recent meta-analysis using cartographic methods estimations 390 million dengue infections per year including 96 million AKT with medical manifestations . This quantity is more than three times higher than the previous dengue burden estimated by the World Health Corporation . With no licensed drug or vaccine, DEN represents a serious public health concern and economic burden for societies. The etiological agent of DEN, dengue disease (DENV), belongs to the genus Flavivirus within the family, which also includes Japanese encephalitis disease (JEV), Western Nile disease (WNV), and yellow fever disease. DENV is an enveloped disease having a single-stranded, positive-sense 10.7 kb RNA genome. It is translated as a single polyprotein that is cleaved by viral and sponsor proteases into three structural proteins (capsid [C], pre-membrane/membrane [prM/M] and envelope [E], and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) . You will find four antigenically unique serotypes of DENV (DENV1-4) that may co-circulate in the same geographical area , . The disease is primarily transmitted to humans from the highly urbanised female mosquito which has spread globally due to improved trade and travel . D-106669 Human being illness with one of the.