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

Abstract

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

Date of Award	2018 Aug 8
Original language	English
Supervisor	Chi-Chang Shieh (Supervisor)