Longitudinal multiomic profiling and corticosteroid modulation of the immediate innate immune response to an adenovirus-vector vaccine.

Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.

The antioxidant enzyme Peroxiredoxin-1 controls stroke-associated microglia against acute ischemic stroke.

Ischemic stroke is the leading cause of immortal disability and death worldwide. For treatment in the acute phase, it is necessary to control excessive reactive oxygen species (ROS) damage during ischemia/reperfusion (I/R). Microglia are well known to be closely associated with excessive ROS response in the early stage of I/R. However, the precise roles of microglia associated with mitigating ROS damage, and molecular markers of heterogenetic microglia in the I/R damaged brain has not been clarified. Here, we identified a new type of microglia associated with stroke in the I/R injured brain. Single-cell RNA sequencing (scRNA-seq) was used to assess transcriptional changes of microglia and immune cells in the contralateral (CL) and ipsilateral (IL) hemispheres after transient middle cerebral artery occlusion (tMCAO) surgery to mimic ischemic stroke. We classified a unique type of microglia with enhanced antioxidant function and markers similar to those of disease-associated microglia (DAM), designated them as stroke-associated microglia (SAM). The representative antioxidant enzyme, Peroxiredoxin-1 (Prdx1), was predominantly expressed in SAM and mediated ROS defense genes, including Txn1, Srx1, Mt1, and Mt2. In the Prdx1-/- I/R damaged brain, we observed significantly increased infarction, as assessed by TTC staining, and FACS analysis detected severe microglial cell death. Importantly, scRNA transcriptomics data showed that the SAM population was specifically decreased in Prdx1-/- mice and that these mice exhibited decreased ROS damage resistance. Inflammatory responses which were detected by ELISA and qPCR, were also increased in Prdx1-/- IL hemispheres. Finally, Prdx1-dependent antioxidative SAM were found to be essential for increasing the transcription levels of stroke-protective molecules, such as osteopontin and ferritin. A novel microglia type (SAM) is specifically activated in response to stroke I/R injury, and that Prdx1 expression is required for the activation and enhanced antioxidant function of SAM.

Host plant effects on the behaviour and performance of Amblyseius swirskii (Acari: Phytoseiidae).

Biological control in ornamental crops is challenging due to the wide diversity of crops and cultivars. In this study, we tested the hypothesis that trichome density on different host plants influences the behavior and performance of the predatory mite Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae). Behavioural observations of this predator in the presence or absence of prey (western flower thrips, Frankliniella occidentalis Pergande) (Thysanoptera: Thripidae) were done on leaf squares of ornamental plant species differing in trichome density (rose, chrysanthemum and gerbera) and compared to a smooth surface (plastic). Tomato leaves were used to observe the influence of glandular trichomes. The performance of A. swirskii was assessed by measuring predation and oviposition rate. Behaviour of A. swirskii was influenced by plant species. Up to a certain density of trichomes, trichome number had a negative effect on walking speed. It was highest on plastic, followed by rose. No differences were found among chrysanthemum, gerbera and tomato. Walking speed was slightly higher on disks without prey. Proportion of time spent walking was the same on leaf disks of all plant species, with and without prey. No effect of glandular trichomes on tomato leaves was seen. Most thrips were killed and consumed on gerbera, and least on rose. Predation rates on chrysanthemum and plastic were intermediate. In contrast, no differences in oviposition rate were found among plant species. The results of this study indicate that trichome density can explain some of the variability in efficacy of A. swirskii on different crops. Release rates of A. swirskii may need to be adjusted depending on the crop in which it is used.

7-ketocholesterol induces endoplasmic reticulum stress in HT-29 cells.

7-Ketocholesterol (7-Kchol, oxidized cholesterol) is an important mediator of cell death in atherosclerosis mediated by up-regulated Nox 4 gene expression. In the current study using the human colon cancer HT-29 cell line, we have demonstrated that 7-Kchol promotes endoplasmic reticulum (ER) stress via gene up-regulation of ER chaperone and membrane kinases.