Mitochondrial and lysosomal activities are crucial to maintain cellular homeostasis: optimal coordination is achieved at their membrane contact sites where distinct protein machineries regulate organelle network dynamics, ions and metabolites exchange. Here we describe a genetically encoded SPLICS reporter for short- and long- juxtapositions between mitochondria and lysosomes. We report the existence of narrow and wide lysosome-mitochondria contacts differently modulated by mitophagy, autophagy and genetic manipulation of tethering factors.
View Article and Find Full Text PDFBackground: Severe COVID-19 is associated with an excessive immunothrombotic response and thromboinflammatory complications. Vaccinations effectively reduce the risk of severe clinical outcomes in patients with COVID-19, but their impact on platelet activation and immunothrombosis during breakthrough infections is not known.
Objectives: To investigate how preemptive vaccinations modify the platelet-immune crosstalk during COVID-19 infections.
Background: Genetic-based COVID-19 vaccines have proved to be highly effective in reducing the risk of hospitalization and death. Because they were first distributed in a large-scale population, the adenoviral-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome, and the interplay between platelets and vaccinations increasingly gained attention.
Objectives: The objective of this article was to study the crosstalk between platelets and the vaccine-induced immune response.
New-generation mRNA and adenovirus vectored vaccines against SARS-CoV-2 spike protein are endowed with immunogenic, inflammatory and immunomodulatory properties. Recently, BioNTech developed a noninflammatory tolerogenic mRNA vaccine (MOGm1Ψ) that induces in mice robust expansion of antigen-specific regulatory T (Treg) cells. The Pfizer/BioNTech BNT162b2 mRNA vaccine against SARS-CoV-2 is identical to MOGm1Ψ except for the lipid carrier, which differs for containing lipid nanoparticles rather than lipoplex.
View Article and Find Full Text PDFBackground: A rapid immune response is critical to ensure effective protection against COVID-19. Platelets are first-line sentinels of the vascular system able to rapidly alert and stimulate the immune system. However, their role in the immune response to vaccines is not known.
View Article and Find Full Text PDF