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Biology subjects

Eberhardt, N.

Publications and source records attributed to Eberhardt, N..

3 recordsLinked to original sources

MICROBIOTA AT THE CROSS ROAD OF DIET AND HEALTH: HOW DIETARY FATS SHAPE BACTERIAL LAND-SCAPE AND INFLUENCE GLOBAL HEALTH

Host-gut microbiota (GM) interactions play a pivotal role in shaping the delicate balance between health and disease within the human body. The impact of dietary factors, specifically high fat content diets on GM composition has been widely demonstrated. We have previously shown that the constant and sustained administration of Omega-3 fatty acids induced specific changes in GM composition, modulating the immune metabolic response of visceral adipose tissue (VAT) in our mouse model of obesity. We now set out to determine if this effect is Omega-3 dose-dependent. To achieve this, C57BL/6J(B6) mice were fed for 24 weeks with three diets, two with medium content total fat, but different Omega-3 content and a control diet. GM composition, metabolic biomarkers and immune cells in VAT were analyzed. A distinctive segregation of GM composition, a significantly higher proportion of regulatory T cells (CD45+CD4+FoxP3+), Omega-3 dose dependent and increased levels of leptin and cholesterol with no differences in adiponectin values were found in fat fed groups. Simple mediation analyses revealed significant associations between the microbial profile and immunometabolic regulation. To remark is the capacity of Lachnospiraceae UCG- 001 to modulate levels of leptin, glucose, and cholesterol through the stimulation of CD45+CD4+FOXP3+IL10+ cells. Our findings suggest a modulatory effect of omega-3 fatty acids on the microbiota, the metabolism, and the immunoregulatory capacity of VAT, supporting the hypothesis that alteration of the GM composition by omega-3 fatty acids may be a promising approach in managing obesity and associated metabolic diseases.

microbiology↗

SARS-CoV-2 infection triggers pro-atherogenic inflammatory 1 responses in human coronary vessels

COVID-19 patients present higher risk for myocardial infarction (MI), acute coronary syndrome, and stroke for up to 1 year after SARS-CoV-2 infection. While the systemic inflammatory response to SARS-CoV-2 infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques to locally promote inflammation remains unknown. Here, we report that SARS-CoV-2 viral RNA (vRNA) is detectable and replicates in coronary atherosclerotic lesions taken at autopsy from patients with severe COVID-19. SARS-CoV-2 localizes to plaque macrophages and shows a stronger tropism for arterial lesions compared to corresponding perivascular fat, correlating with the degree of macrophage infiltration. In vitro infection of human primary macrophages highlights that SARS-CoV-2 entry is increased in cholesterol-loaded macrophages (foam cells) and is dependent, in part, on neuropilin-1 (NRP-1). Furthermore, although viral replication is abortive, SARS-CoV-2 induces a robust inflammatory response that includes interleukins IL-6 and IL-1{beta}, key cytokines known to trigger ischemic cardiovascular events. SARS-CoV-2 infection of human atherosclerotic vascular explants recapitulates the immune response seen in cultured macrophages, including pro-atherogenic cytokine secretion. Collectively, our data establish that SARS-CoV-2 infects macrophages in coronary atherosclerotic lesions, resulting in plaque inflammation that may promote acute CV complications and long-term risk for CV events.

immunology↗

Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo

Whooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein -subunits resulting in increased cAMP signaling. Here, the role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is characterized in detail. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing cytosolic PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.

pharmacology and toxicology↗