No abstract

Extracellular vesicles (EVs) are the common designation for ectosomes, microparticles and microvesicles serving dominant roles in intercellular communication. Both viable and dying cells release EVs to the extracellular environment for transfer of cell, immune and infectious materials. Defined morphologically as lipid bi-layered structures EVs show molecular, biochemical, distribution, and entry mechanisms similar to viruses within cells and tissues. In recent years their functional capacities have been harnessed to deliver biomolecules and drugs and immunological agents to specific cells and organs of interest or disease. Interest in EVs as putative vaccines or drug delivery vehicles are substantial. The vesicles have properties of receptors nanoassembly on their surface. EVs can interact with specific immunocytes that include antigen presenting cells (dendritic cells and other mononuclear phagocytes) to elicit immune responses or affect tissue and cellular homeostasis or disease. Due to potential advantages like biocompatibility, biodegradation and efficient immune activation, EVs have gained attraction for the development of treatment or a vaccine system against the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection. In this review efforts to use EVs to contain SARS CoV-2 and affect the current viral pandemic are discussed. An emphasis is made on mesenchymal stem cell derived EVs' as a vaccine candidate delivery system.

In animals and humans, offspring of allergic mothers have increased responsiveness to allergen and the allergen-specificity of the offspring can be different than that of the mother. In our preclinical models, the mother's allergic responses influence development of the fetus and offspring by elevating numbers of cells in dendritic cell subsets. A major question is the identity of maternal factors of allergic mothers that alter offspring development of responsiveness to allergen. Lipids are altered during allergic responses and lipids are transported to the fetus for growth and formation of fetal membranes. We hypothesized that pro-inflammatory lipids, that are elevated in allergic mothers, are transported to the fetus and regulate fetal immune development. We demonstrate in this report that there was a significant 2-fold increase in β-glucosylceramides (βGlcCer) in allergic mothers, the fetal liver and her offspring. The βGlcCer were transported from mother's plasma, across the placenta, to the fetus and in breastmilk to the offspring. Administration of βGlcCer to non-allergic mothers was sufficient for offspring responses to allergen. Importantly, maternal administration of a clinically relevant pharmacological inhibitor of βGlcCer synthase returned βGlcCer to normal levels in the allergic mothers and her offspring and blocked the offspring increase in dendritic cell subsets and offspring allergen responsiveness. In summary, allergic mothers had increased βGlcCer that was transported to offspring and mediated increases in offspring DCs and responsiveness to allergen. These data have a significant impact on our understanding of mechanisms for development of allergies in offspring of allergic mothers and have the potential to lead to novel interventions that significantly impact risk for allergic disease early in life.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to coronavirus disease 2019 (COVID-19). Virus-specific immunity controls infection, transmission, and disease severity. With respect to disease severity, a spectrum of clinical outcomes can occur on the basis of the age, genetics, comorbidities, and immune responses in an infected person. Dysfunctions in innate and adaptive immunity commonly follow viral infection. These are heralded by altered mononuclear phagocyte differentiation, activation, intracellular killing and memory, effector, and regulatory T cell responses. All of such affect viral clearance and the progression of end-organ disease. Failures to produce effective controlled antiviral immunity leads to life-threatening end-organ disease that is typified by the acute respiratory distress syndrome. The most effective means to contain SARS-CoV-2 infection is by vaccination. While an arsenal of immunomodulators were developed for control of viral infection and subsequent COVID-19 disease, further research is required to enable therapeutic implementation.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Pathologically, the disease is characterized by the deposition of amyloid beta (Aβ) plaques and the presence of neurofibrillary tangles. These drive microglia neuroinflammation and consequent neurodegeneration. While the means to affect Aβ plaque accumulation pharmacologically was achieved, how it affects disease outcomes remains uncertain. Cerium oxide (CeO 2 ) reduces Aβ plaques, oxidative stress, inflammation, and AD signs and symptoms. In particular, CeO 2 nanoparticles (CeO 2 NPs) induce free-radical-scavenging and cell protective intracellular signaling. This can ameliorate the pathobiology of an ADaffected brain. To investigate whether CeO 2 NPs affect microglia neurotoxic responses, a novel formulation of europium-doped CeO 2 NPs (Eu-CeO 2 NPs) was synthesized. We then tested EuCeO 2 NPs for its ability to generate cellular immune homeostasis in AD models. EuCeO 2 NPs attenuated microglia BV2 inflammatory activities after Aβ 1−42 exposure by increasing the cells' phagocytic and Aβ degradation activities. These were associated with increases in the expression of the CD36 scavenger receptor. EuCeO 2 NPs facilitated Aβ endolysosomal trafficking and abrogated microglial inflammatory responses. We posit that EuCeO 2 NPs may be developed as an AD immunomodulator.