The immunopathogensis underlying the higher severity and mortality in dengue virus infection in diabetes mellitus

• Main Authors: Sung-LinLiu, 劉松林
• Other Authors: Chi-Chang Shieh
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/9xbntc

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 106 === Dengue virus is a blood-borne pathogen that causes dengue fever in patients. In the primary dengue virus infection, the virus usually causes mild dengue fever. In the secondary infection, however, the virus can induce life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which lead to plasma leakage and hemorrhage by causing thrombocytopenia and increased vascular permeability. Our previous studies showed that patients with diabetes mellitus (DM) are immunodeficient due to aberrant immune signal transduction and their innate immune cells were severely weakened in the responses to certain infections. The data from the previous epidemic also showed that dengue patients with DM had higher viral loads and a higher chance of severe disease in comparison with patients without DM. Therefore, we investigated the immune responses to primary dengue viral infection in a diabetic mouse model. We found enhanced vascular permeability in the liver and small intestine of the STAT1-/- mouse with dengue virus infection. We also observed hemorrhage and leukocyte infiltration in the small intestine of STAT1-/- mice with dengue virus infection. We then intravenously infected the streptozotocin (STZ)-induced diabetic mouse. We found enhanced vascular permeability in the small intestine of the diabetic mouse infected with dengue virus. We also investigated the changes in innate lymphoid cells (ILCs) in the primary dengue virus-infected diabetic mice model. We found increased ILC1 and ILC3 in the small intestine of the diabetic mouse infected with dengue virus. The abnormal immune responses in subjects with DM hence may be similar to the immunodeficient conditions reported to predispose to more severe dengue virus infection.