Crestani, E. | Search bioRxiv

bioRxiv2021

A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV2 at the immune-epithelial interface

Infection by SARS-CoV2 provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled by in vitro co-culture the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV2-specific inflammatory gene cluster distinct from that seen in influenza-A or Ebola virus-infected co-cultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV2 proteins (Spike and some non-structural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age-dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV2 induces in epithelia.

immunology↗

bioRxiv2019

Untargeted Metabolomic Profiling Identifies Disease-specific Profiles in Food Allergy

BackgroundFood allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Identification of pathogenic mechanisms involved in FA using untargeted metabolomic approaches may provide much needed diagnostic and prognostic disease biomarkers and improved treatment options.\n\nMethodsMass spectrometry-based untargeted metabolomic profiling was performed on serum samples of children with either FA alone, asthma alone or both FA and asthma as well as healthy pediatric controls.\n\nResultsFA subjects exhibited a disease-specific metabolomic signature as compared to both control subjects and asthmatics. In particular, FA was uniquely associated with a marked decrease in sphingolipids, as well as a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T (NKT) cells. Specific comparison of FA and asthmatic subjects revealed differences in the microbiota-sensitive aromatic amino acid and secondary bile acid metabolism. Children with both FA and asthma exhibited a metabolomic profile that aligned with that of FA alone but not asthma. Among children with FA, distinct profiles were associated with history of severe reactions and presence of multiple FA.\n\nConclusionsChildren with FA display a disease-specific metabolomic profile that is informative of disease mechanisms and severity, and which dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in FA children may reflect the interplay between an altered microbiota and immune cell subsets in the gut.

immunology↗