Norketamine [KLH]

BackgroundThe immune mechanisms that determine whether a Plasmodium falciparum infection would be symptomatic or asymptomatic are not fully understood. Several studies have been carried out to characterize the associations between disease outcomes and leucocyte numbers. However, the majority of these studies have been conducted in adults with acute uncomplicated malaria, despite children being the most vulnerable group.MethodsPeripheral blood leucocyte subpopulations were characterized in children with acute uncomplicated (symptomatic; n=25) or asymptomatic (n=67) P. falciparum malaria, as well as malaria-free (uninfected) children (n=16) from Obom, a sub-district of Accra, Ghana. Leucocyte subpopulations were enumerated by flow cytometry and correlated with two measures of parasite load: (a) plasma levels of P. falciparum histidine-rich protein 2 (PfHRP2) as a proxy for parasite biomass and (b) peripheral blood parasite densities determined by microscopy.ResultsIn children with symptomatic P. falciparum infections, the proportions and absolute cell counts of total (CD3+) T cells, CD4+T cells, CD8+T cells, CD19+B cells and CD11c+dendritic cells (DCs) were significantly lower as compared to asymptomatic P. falciparum-infected and uninfected children. Notably, CD15+neutrophil proportions and cell counts were significantly increased in symptomatic children. There was no significant difference in the proportions and absolute counts of CD14+monocytes amongst the three study groups. As expected, measures of parasite load were significantly higher in symptomatic cases. Remarkably, PfHRP2 levels and parasite densities negatively correlated with both the proportions and absolute numbers of peripheral leucocyte subsets: CD3+T, CD4+T, CD8+T, CD19+B, CD56+NK, gamma delta +T and CD11c+cells. In contrast, both PfHRP2 levels and parasite densities positively correlated with the proportions and absolute numbers of CD15+cells.ConclusionsSymptomatic P. falciparum infection is correlated with an increase in the levels of peripheral blood neutrophils, indicating a role for this cell type in disease pathogenesis. Parasite load is a key determinant of peripheral cell numbers during malaria infections.

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.