Dynamics of circulating lymphocytes responding to human experimental enterotoxigenic Escherichia coli infection.

Enterotoxigenic Escherichia coli (ETEC) is an important cause of children's and travelers' diarrhea, with no licensed vaccine. This study aimed to explore the role of cellular immunity in protection against human ETEC infection. Nine volunteers were experimentally infected with ETEC, of which six developed diarrhea. Lymphocytes were collected from peripheral blood buffy coats, before and 3, 5, 6, 7, 10, and 28 days after dose ingestion, and 34 phenotypic and functional markers were examined by mass cytometry. Thirty-three cell populations, derived by manually merging 139 cell clusters from the X-shift unsupervised clustering algorithm, were analyzed. Initially, the diarrhea group responded with increased CD56dim CD16+ natural killer cells, dendritic cells tended to rise, and mucosal-associated invariant T cells decreased. On day 5-7, an increase in plasmablasts was paralleled by a consistent rise in CD4+ Th17-like effector memory and regulatory cell subsets. CD4+ Th17-like central memory cells peaked on day 10. All Th17-like cell populations showed increased expression of activation, gut-homing, and proliferation markers. Interestingly, in the nondiarrhea group, these same CD4+ Th17-like cell populations expanded earlier, normalizing around day 7. Earlier development of these CD4+ Th17-like cell populations in the nondiarrhea group may suggest a recall response and a potential role in controlling ETEC infections.

Innate Immune Mechanism of Neutrophil Extracellular Trap Formation is Impaired in at-Risk Term Low Birth Weight Newborns.

Low birth weight (LBW) is a leading cause of newborn's mortality however the underlying defects in cellular immunity and immune mechanisms leading to severe neonatal infections in term LBW (tLBW) newborns are not well understood. Neutrophil extracellular traps (NETs), or NETosis, is an innate immune defense mechanism of neutrophils involved in trapping and killing of microbes. The efficiency of NET formation in cord blood derived neutrophils of tLBW and normal birth weight (NBW) newborns in the presence of toll like receptor (TLR) agonist inductions was evaluated. The NET formation was observed to be substantially impaired in tLBW newborns along with NET proteins expression, extracellular deoxyribonucleic acid (DNA) release and reactive oxygen species generation. The placental tissues from tLBW newborns delivery also showed minimal NETosis. These findings suggest impaired NET formation to be an important factor underlying the deficient immune status of tLBW newborns making them susceptible to life- threatening infections.

Potential antianxiety activity of Fumaria indica: A preclinical study.

BACKGROUND: In the view of diverse CNS modulating properties of Fumaria indica, present study was planned to evaluate its putative anxiolytic activity in behavioural models of rats, followed by elucidation of mechanism of observed activity through biochemical estimations. MATERIALS AND METHODS: Effects of seven daily 100, 200 and 400 mg/kg oral doses of a Fumaria indica extract (FI) was compared with those of an acute oral dose (5 mg/kg) of lorazepam in a battery of rat models consisting of open-field, elevated plus and zero maze, social interaction, and novelty induced feeding tests. RESULTS: Dose dependant antianxiety effects of FI observed in all tests were qualitatively similar to those of the reference anxiolytic drug. Although FI treatments did not alter the concentrations of noradrenaline and serotonin in hippocampus and hypothalamus, concentrations of both these monoamines were dose dependently elevated in prefrontal cortex of FI treated animals. Flunitrazepam binding in brain frontal cortex was also elevated by the extract. Moreover, higher levels of brain expressions of the cytokines TNF-α, IL-1ß, and IL-10 observed in animals with prior experience on elevated plus maze were almost completely reversed by the lowest dose of FI tested in the behavioral models. CONCLUSION: Taken together, these observations strongly suggest that FI is a functionally novel type of antianxiety agent, and that inhibition of cytokine expressions in the brain could be involved in its mode of action.