CNS Immune Profiling in a Dengue Virus-Infected Immunocompetent Outbred ICR Mice Strain

Abstract

Dengue virus (DENV) infection in the brain causes severe dengue disease with neuropathic complications. In addition to viral effects, immunogenic or pathogenic central nervous system (CNS) inflammation can be induced during DENV infection. By using an immunocompetent outbred ICR (Institute of Cancer Research) mouse model for investigating CNS immunity upon DENV infection, we conducted single-panel immune cell profiling and a multiplex cytokine assay. The ICR mice infected with DENV presented with progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality. When the virions were released, the viral non-structural protein 1 was expressed in the brain in a time-dependent manner. Isolated brain CD45-positive cells revealed a significant population of resident CD14-positive cells, which was considerably decreased 8 days post-infection. We found an unexpected time-kinetic decrease in CD19-positive cells and CD11c/MHC II-positive cells and an increase in NK1.1-positive cells. Further assays showed the time-dependent induction of proinflammatory and NK1.1-associated cytokines in the DENV-infected brains. These results indicate a CNS immune profile of DENV infection and hypothetical CNS immunity in response to DENV infection.

Serum IL-18 Is a Potential Biomarker for Predicting Severe Dengue Disease Progression

“…Meanwhile, the older severity classification from 1997 differs between classifications for mild dengue fever (MDF) and severe dengue disease (SDD) through the presence of plasma leakage. The MDF and SDD terms used refer to the previous publication, where the severe dengue disease encompassed dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [ 25 ]. Therefore, according to the WHO classification, both WHO severity criteria from 1997 to 2009 are acceptable, as long as the article can define the severity differences of MDF and SDD.…”

Antiviral Efficacy of the Anesthetic Propofol against Dengue Virus Infection and Cellular Inflammation

“…The process of cell culture and virus preparation was according to our previous study [ 10 ]. Briefly, baby hamster kidney- (BHK-) 21 fibroblasts (ATCC, CCL10) were maintained in Dulbecco's modified Eagle's medium (DMEM; Thermo Fisher Scientific) containing 10% heat-inactivated fetal bovine serum (FBS, Biological Industries) and 1% penicillin-streptomycin (Thermo Fisher Scientific) at 37°C in 5% CO 2 .…”

“…Accordingly [ 10 ], cells were collected and extracted with lysis buffer containing a protease inhibitor cocktail (Sigma-Aldrich). The processed proteins were separated by 10% SDS-polyacrylamide gel electrophoresis followed by transfer to a polyvinylidene difluoride (PVDF) membrane (Millipore).…”

Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus

“…Flavivirus infections are reported to cause blood-brain barrier (BBB) destruction [26][27][28][29][30]. Previous reports indicate kinetic changes in peripheral macrophage infiltration and inflammatory factor secretion in the brain after DENV infection [31]. According to the previous experimental encephalitis-like models of DENV infection in the immunocompetent mice [12,15,16], similar and conditional procedures of the infectious route have been performed to investigate immune activation and microglia/macrophage polarization during flavivirus-induced encephalitis-like disease.…”