Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation

Distinct dendritic cell (DC) subsets have been suggested to be preprogrammed to direct either T helper cell (Th) type 1 or Th2 development, although more recently different pathogen products or stimuli have been shown to render these DCs more flexible. It is still unclear how distinct mouse DC subsets cultured from bone marrow precursors, blood, or their lymphoid tissue counterparts direct Th differentiation. We show that mouse myeloid and plasmacytoid precursor DCs (pDCs) cultured from bone marrow precursors and ex vivo splenic DC subsets can induce the development of both Th1 and Th2 effector cells depending on the dose of antigen. In general, high antigen doses induced Th1 cell development whereas low antigen doses induced Th2 cell development. Both cultured and ex vivo splenic plasmacytoid-derived DCs enhanced CD4(+) T cell proliferation and induced strong Th1 cell development when activated with the Toll-like receptor (TLR)9 ligand CpG, and not with the TLR4 ligand lipopolysaccharide (LPS). The responsiveness of plasmacytoid pDCs to CpG correlated with high TLR9 expression similarly to human plasmacytoid pDCs. Conversely, myeloid DCs generated with granulocyte/macrophage colony-stimulating factor enhanced Th1 cell development when stimulated with LPS as a result of their high level of TLR4 expression. Polarized Th1 responses resulting from high antigen dose were not additionally enhanced by stimulation of DCs by TLR ligands. Thus, the net effect of antigen dose, the state of maturation of the DCs together with the stimulation of DCs by pathogen-derived products, will determine whether a Th1 or Th2 response develops.     

Illustration of the Difficulty of Identifying Streptococcus equi Strains at the Subspecies Level through a Case of Endocarditis in an Immunocompetent Man

We report a case of endocarditis caused by Streptococcus equi in an immunocompetent patient who was subsequently cured after appropriate antibiotherapy and cardiac surgery. However, it was challenging to identify the strain to the subspecies level, which highlights the necessity of developing reliable molecular tools to discriminate between the subspecies.     

Metabolic changes detected in vivo by 1H MRS in the MPTP‐intoxicated mouse

We used in vivo proton (¹H) Magnetic Resonance Spectroscopy (MRS) to measure the levels of the main excitatory amino acid, glutamate (Glu) and also glutamine (Gln) and GABA in the striatum and cerebral cortex in the MPTP‐intoxicated mouse, a model of dopaminergic denervation, before and after dopamine (DA) replacement. The study was performed at 9.4T on control mice (n = 8) and MPTP‐intoxicated mice (n = 8). In vivo spectra were acquired in a voxel (8 µL) centered in the striatum, and in the cortex (4.6 µL). Three days after basal MRS acquisitions new spectra were acquired in the striatum and cortex, after levodopa (200 mg.kg^?1). Glu, Gln and GABA concentrations obtained in the basal state were significantly increased in the striatum of MPTP‐lesioned mice (Glu: 20.2 ± 0.8 vs 11.4 ± 0.9 mM, p < 0.001; Gln: 5.4 ± 1.6 vs 2.0 ± 0.6 mM, p < 0.05; GABA: 3.6 ± 0.8 vs 1.6 ± 0.2 mM, p < 0.05). Levodopa lowered metabolites concentrations in the striatum of MPTP‐lesioned mice (Glu: 20.2 ± 0.8 vs 11.2 ± 0.4 mM (+ Ldopa), p < 0.001; Gln: 5.4 ± 1.6 vs 1.6 ± 0.4 mM (+ Ldopa), p < 0.05; GABA: 3.6 ± 0.8 vs 1.7 ± 0.4 mM (+ Ldopa), p < 0.01). Metabolite levels in the striatum of MPTP‐intoxicated mice + levodopa were not significantly different from those in the striatum of controls. No change was found in the cortex after DA denervation and after DA replacement between the two animals groups. These results strongly support a predominant change in striatal Glu synaptic activity in the cortico‐striatal pathway. Acute levodopa administration reverses the increase of metabolites in the striatum. Copyright © 2010 John Wiley & Sons, Ltd.     

Deprescribing clonazepam in primary care older patients: a feasibility study

International Journal of Clinical Pharmacy - Background Inappropriate use of clonazepam by older adults is associated with cognitive impairment, delirium, and falls. Strategies to optimize its use...