Early macrophage response to obesity encompasses Interferon Regulatory Factor 5 regulated mitochondrial architecture remodelling

International audienceAbstract Adipose tissue macrophages (ATM) adapt to changes in their energetic microenvironment. Caloric excess, in a range from transient to diet-induced obesity, could result in the transition of ATMs from highly oxidative and protective to highly inflammatory and metabolically deleterious. Here, we demonstrate that Interferon Regulatory Factor 5 (IRF5) is a key regulator of macrophage oxidative capacity in response to caloric excess. ATMs from mice with genetic-deficiency of Irf5 are characterised by increased oxidative respiration and mitochondrial membrane potential. Transient inhibition of IRF5 activity leads to a similar respiratory phenotype as genomic deletion, and is reversible by reconstitution of IRF5 expression. We find that the highly oxidative nature of Irf5 -deficient macrophages results from transcriptional de-repression of the mitochondrial matrix component Growth Hormone Inducible Transmembrane Protein (GHITM) gene. The Irf5 -deficiency-associated high oxygen consumption could be alleviated by experimental suppression of Ghitm expression. ATMs and monocytes from patients with obesity or with type-2 diabetes retain the reciprocal regulatory relationship between Irf5 and Ghitm . Thus, our study provides insights into the mechanism of how the inflammatory transcription factor IRF5 controls physiological adaptation to diet-induced obesity via regulating mitochondrial architecture in macrophages

Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID ‐19 in type 2 diabetes

International audienceEarly in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at-risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study charac-terised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lympho-cytopenia and specific loss of cytotoxic CD8 + lymphocytes were associated with severe COVID-19 and requirement for intensive care in both non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14 Hi CD16 À monocytes was specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID-19 in T2D. These findings allow precise identification of T2D patients with severe COVID-19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies

De morcegos e caveiras a cruzes e livros: a representação da morte nos cemitérios cariocas do século XIX (estudo de identidade e mobilidade soclais)

Considerando que os espaços destinados aos mortos em uma sociedade refletem especularmente o mundo dos vivos, sendo ambos regidos pela mesma lógica de organização, os cemitérios foram entendidos como um lugar de reprodução simbólica do universo social, e, nessa condição, como um campo privilegiado para a análise do processo de implantação e consolidação dos val-ores burgueses na socieaade carioca do século passado. O presente trabalho, considerando a ruptura do império escravista, na década de 1880, e a emergência de uma república progressivamente capitalista, voltou-se para a verificação de prováveis mudanças no imaginário coletivo sobre a morte, nos cemitérios do Rio de Janeiro, provocadas pelo rompimento aa ordem escravocrata. Uma pesquisa foi conduzida no sentido de se investigar não apenas a natureza dessa mudança, mas sobretudo os mecanismos subjacentes que a determinaram, sendo aqui apresentados os seus resultados