Schistosome infection is associated with enhanced whole-blood IL-10 secretion in response to cercarial excretory/secretory products.

Infection of the human host by schistosome parasites follows exposure of skin to free-swimming cercariae and is aided by the release of excretory/secretory (E/S) material, which is rich in proteases and glycoconjugates. This material provides the initial stimulus to cells of the innate immune system. The study presented here is the first to examine human innate/early immune responsiveness to cercarial E/S in subjects from an area co-endemic for Schistosoma mansoni and S. haematobium. We report that in infected participants, stimulation of whole-blood cultures with cercarial E/S material (termed 0-3 hRP) caused the early (within 24 h) release of greater quantities of regulatory IL-10, compared with uninfected controls. Elevated levels of IL-10 but not pro-inflammatory TNFα or IL-8 were most evident in participants co-infected with S. mansoni and S. haematobium and were accompanied by a higher 0-3 h RP-specific IL-10: TNFα ratio. We also report that glycosylated components within 0-3 h RP appear to be important factors in the stimulation of IL-8, TNFα and IL-10 production by whole-blood cells.

Time-dependent regulation of yeast glycolysis upon nitrogen starvation depends on cell history.

In this study, the authors investigated how the glycolytic flux was regulated in time upon nitrogen starvation of cells with different growth histories. We have compared cells grown in glucose-limited chemostat cultures under respiratory conditions (low dilution rate of 0.1/h) to cells grown under respirofermentative conditions (high dilution rate of 0.35/h). The fermentative capacity was lower in cells grown under respiratory conditions than in cells grown under respirofermentative conditions, yet more resilient to prolonged nitrogen starvation. The time profiles revealed that the fermentative capacity even increased in cells grown under respiratory conditions during the first hours of nitrogen starvation. In cells grown under respirofermentative conditions the fermentative capacity decreased from the onset of nitrogen starvation. We have applied time-dependent Regulation Analysis to follow the fermentative capacity during nitrogen starvation. In both experiments, diverse categories of regulation were found. However, in the cells grown under respiratory conditions regulation was predominantly metabolic, whereas in the cells grown under respirofermentative conditions hierarchical regulation was dominant. To study the metabolic regulation, concentrations of intracellular metabolites, including allosteric regulators, were measured. The obtained results can explain some aspects of the metabolic regulation, but not all.