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Goossens, P.

Publications and source records attributed to Goossens, P..

4 recordsLinked to original sources

Atherosclerotic plaque iron accumulation characterizes a distinct phase of intra-plaque hemorrhage and is associated with inflammation and remodeling

Intraplaque haemorrhage (IPH) is a hallmark of advanced atherosclerosis and a major risk factor for ischemic stroke and myocardial infarction. Current IPH classification focusses on extravascular erythrocyte presence as a proxy of acute bleeding, where iron detection generally indicates older haemorrhages. While often used interchangeably, a comprehensive analysis of transcriptional and metabolic context and impact of iron and erythrocyte deposition on the plaque is still lacking. Here, we investigate iron as a late-stage IPH hallmark in human atherosclerotic plaques. We analysed erythrocyte-rich, iron-rich, and non-IPH regions in human carotid endarterectomy plaques by re-analysing a published transcriptomic dataset of 43 patient samples. In addition, we performed histological and immune phenotyping to define plaque traits associated with iron versus erythrocyte accumulation. Finally, we performed spatial metabolic profiling to functionally define iron-rich regions. Although iron and erythrocyte deposits frequently co-localised, both co-related with different histological traits. While iron- and erythrocyte-rich regions shared transcriptomic features of advanced plaques compared with non-IPH regions, direct comparison showed differences in gene expression profiles. Iron deposition was associated with increased myeloid cell accumulation and a unique spatial metabolic signature distinct from erythrocyte-rich and non-IPH regions. While sharing many characteristics with IPH plaques, the molecular, cellular and metabolic landscape of iron-rich regions is marked by features of plaque remodelling and repair. This makes iron deposition a unique hallmark of late-stage IPH, extending the current erythrocyte-based definition of IPH.

pathology↗

Selective enrichment of specific bacterial taxa in downy mildew-affected spinach: Comparative analysis in laboratory and field conditions

Plants host diverse microbial communities that can be influenced by their hosts to mitigate biotic stress. Previous research demonstrated that distinct laboratory cultures of Hyaloperonospora arabidopsidis (Hpa) on Arabidopsis thaliana, consistently harbor nearly identical bacteria. In this study, we analyzed the bacterial phyllosphere communities of laboratory-grown spinach plants infected by the downy mildew pathogen Peronospora effusa (Pe). Using 16S amplicon sequencing, we identified 14 Amplicon Sequence Variants (ASVs), with diverse taxonomies, that were enriched in at least 3 out of 5 investigated Pe cultures. This small set of 14 ASVs occupied on average 6.9% of the total bacterial communities in healthy spinach plants, and 43.1% in Pe-inoculated plants. A specific Rhodococcus and a Paenarthrobacter ASV were particularly prevalent and abundant. To validate these findings outside of the laboratory, we planted a susceptible variety of spinach in 4 agricultural fields and sampled leaves from Pe-infected plants in 2 fields where this pathogen naturally occurred. Comparative microbiome analysis of diseased and healthy plants revealed significant enrichment of 16 and 31 ASVs in these 2 fields, respectively. Among these, the Paenarthrobacter ASV was enriched in one field and the Rhodococcus ASV in the other field, suggesting that disease-associated microbiota that are abundantly detected in Pe laboratory cultures are also associated with Pe-infected field plants. Additionally, we observed an overlap of ASVs that were associated with both Pe and Hpa, indicating that similar bacteria are linked to downy mildew disease across different hosts.

microbiology↗

Congruent downy mildew-associated microbiomes reduce plant disease and function as transferable resistobiomes

Root-associated microbiota can protect plants against severe disease outbreaks. In the model-plant Arabidopsis thaliana, leaf infection with the obligate downy mildew pathogen Hyaloperonospora arabidopsidis (Hpa) results in a shift in the root exudation profile, therewith promoting the growth of a selective root microbiome that induces a systemic resistance against Hpa in the above-ground plant parts. Here we show that, additionally, a conserved subcommunity of the recruited soil microbiota becomes part of a pathogen-associated microbiome in the phyllosphere that is vertically transmitted with the spores of the pathogen to consecutively infected host plants. This subcommunity of Hpa-associated microbiota (HAM) limits pathogen infection and is therefore coined a "resistobiome". The HAM resistobiome consists of a small number of bacterial species and was first found in our routinely maintained laboratory cultures of independent Hpa strains. When co-inoculated with Hpa spores, the HAM rapidly dominates the phyllosphere of infected plants, negatively impacting Hpa spore formation. Remarkably, isogenic bacterial isolates of the abundantly-present HAM species were also found in strictly separated Hpa cultures across Europe, and even in early published genomes of this obligate biotroph. Our results highlight that pathogen-infected plants can recruit protective microbiota via their roots to the shoots where they become part of a pathogen-associated resistobiome that helps the plant to fight pathogen infection. Understanding the mechanisms by which pathogen-associated resistobiomes are formed will enable the development of microbiome-assisted crop varieties that rely less on chemical crop protection.

microbiology↗

Pharmacological depletion of microglia prevents vascular cognitive impairment in Ang II-induced hypertension

Rationale: Hypertension is a major risk factor for cerebral small vessel disease, the most prevalent cause of vascular cognitive impairment. As we have shown, hypertension induced by a prolonged Ang II infusion is associated with increased permeability of the blood-brain barrier (BBB) and chronic activation of microglia. In this study we therefore aim to determine the contribution of microglia to hypertension-induced cognitive impairment in an experimental hypertension model by a pharmacological depletion approach. Methods: For this study, adult Cx3Cr1gfp/wtxThy1yfp/0 reporter mice were infused for 12 weeks with Angiotensin II or saline and subgroups were treated with PLX5622, a highly selective CSF-1R inhibitor. Systolic blood pressure (SBP) was measured via tail-cuff. Short- and long-term spatial memory were assessed during an Object Location task and a Morris Water Maze task (MWM). At the end of the study, microglia depletion efficacy and BBB leakages were assessed using flow cytometry and immunohistochemistry. Results: SBP, heart weight and carotid pulsatility were increased by Ang II and were not affected by PLX5622. Short-term memory was significantly impaired in Ang II hypertensive mice, but not in Ang II mice treated with PLX5622. Histological and flow cytometry analyses revealed almost complete ablation of microglia upon CSF1R inhibition, while brain resident perivascular macrophages, were reduced by 60%. Number and size of BBB leakages were increased in Ang II hypertensive mice, but not altered by PLX5622 treatment. Conclusion: Our results show that depletion of microglia, and less so PVMs, by CSF1R inhibition prevents short-term memory impairment in Ang II induced hypertensive mice. This novel finding supports the critical role of brain immune cells, and most in particular microglia, in the pathogenesis of hypertension-related cognitive impairment.

neuroscience↗