Gold nanoparticles (GNPs) are claimed as outstanding biomedical tools for cancer diagnostics and photo-thermal therapy, but without enough evidence on their potentially adverse immunological effects. Using a model of human dendritic cells (DCs), we showed that 10 nm- and 50 nm-sized GNPs (GNP10 and GNP50, respectively) were internalized predominantly via dynamin-dependent mechanisms, and they both impaired LPS-induced maturation and allostimulatory capacity of DCs, although the effect of GNP10 was more prominent. However, GNP10 inhibited LPS-induced production of IL-12p70 by DCs, and potentiated their Th2 polarization capacity, while GNP50 promoted Th17 polarization. Such effects of GNP10 correlated with a stronger inhibition of LPS-induced changes in Ca2+ oscillations, their higher number per DC, and more frequent extra-endosomal localization, as judged by live-cell imaging, proton, and electron microscopy, respectively. Even when released from heat-killed necrotic HEp-2 cells, GNP10 inhibited the necrotic tumor cell-induced maturation and functions of DCs, potentiated their Th2/Th17 polarization capacity, and thus, impaired the DCs' capacity to induce T cell-mediated anti-tumor cytotoxicity in vitro. Therefore, GNP10 could potentially induce more adverse DC-mediated immunological effects, compared to GNP50.
Vaccination is one of the most important methods of prevention of infectious disease, saving millions of lives worldwide and protecting people from potentially debilitating complications. It is therefore hailed as one of the greatest advances of science-based medicine of all times. Although repeatedly proven safe and effective, vaccination has been questioned and resented throughout its long history. Vaccine hesitancy and refusal are once again on the rise in this century, due to a complex interplay of numerous factors and circumstances. A decline in childhood vaccination rates has already resulted in resurgence of hitherto eliminated vaccinepreventable diseases in many countries, and is now perceived as a major public health threat. This decline is closely related to increasing spread of misinformation regarding vaccine safety and effectiveness, coupled with a growing anti-vaccine activism. This, among other issues, underscores the need to improve communication between healthcare workers and parents, as well as devise a more comprehensive approach to boosting vaccine confidence, where scientists, physicians, media and the general public all have important roles to play. In this paper, we discuss the phenomenology and causal structure of vaccine hesitancy and refusal, and briefly review some widespread vaccine-related questions of everyday practical importance.
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