BCG vaccination protects not only against tuberculosis but also against heterologous infections. This effect differs between individuals, yet the factors responsible for this variation are unknown. BCG-induced nonspecific protection is, at least partially, mediated by innate immune reprogramming (trained immunity), which can be induced by the muramyl dipeptide (MDP) component of peptidoglycans. We aimed to study whether differential release of MDP in healthy individuals may explain variability of their response to BCG vaccination. Circulating MDP concentrations were increased up to three months after BCG vaccination. MDP concentrations at baseline, but not their increase postvaccination, positively correlated with the induction of trained immunity and not with mycobacteria-induced T-cell responses. Interestingly, MDP concentrations correlated with inflammatory markers in the circulation. In conclusion, circulating MDP concentrations are associated with the strength of trained immunity responses and thus influence the biological effects of BCG vaccination. This study increases our understanding about the role of MDP in BCG-induced trained immunity, which might help to optimize vaccine efficacy and explore novel applications of BCG vaccination.
In this study, we prepared a series of lutein nanodispersions via the solvent displacement method, by using surfactants with different stabilizing mechanisms. The surfactants used include Tween 80 (steric stabilization), sodium dodecyl sulfate (SDS; electrostatic stabilization), sodium caseinate (electrosteric stabilization) and SDS-Tween 80 (electrostatic-steric stabilization). We then characterized the resulting lutein nanodispersions in terms of their particle size, particle size distribution, zeta potential, lutein content, flow behavior, apparent viscosity, transmittance, color, morphological properties and their effects on cell viability and cellular uptake. The type of surfactant used significantly (p < 0.05) affected the physical properties of the nanodispersions, but the chemical properties (lutein content) remained unaffected. Transmission electron microscopy (TEM) images obtained from this study demonstrated that the solvent displacement method was capable of producing lutein nanodispersions containing spherical particles with sizes ranging from 66.20-125.25 nm, depending on the type of surfactant used. SDS and SDS-Tween 80 surfactants negatively affected the viability of the HT-29 cells used in this study. Thus, for the cellular uptake determination, only Tween 80 and sodium caseinate surfactants were used. The cellular uptake of the lutein nanodispersion stabilized by sodium caseinate was higher than that which was stabilized by Tween 80. All things considered, the type of surfactant with different stabilizing mechanisms did produce lutein nanodispersions with different characteristics. These findings would aid in future selection of surfactants in order to produce nanodispersions with desirable properties.
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