TY - JOUR T1 - Macrophage aggresome-like induced structures are flexible organizing platforms for immune signaling JF - bioRxiv DO - 10.1101/2020.11.30.398750 SP - 2020.11.30.398750 AU - Marie-Eve Charbonneau AU - Vedhika Raghunathan AU - Mary X.D. O’Riordan Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/12/01/2020.11.30.398750.abstract N2 - Macrophages adopt a pro-inflammatory phenotype in response to environmental challenges in a process that often coincides with the formation of transient cytosolic p62/SQSTM1 inclusions containing ubiquitinated proteins in structures known as aggresome-like induced structures (ALIS). Although described as stress-induced inclusions that accumulate aggregated proteins, little direct evidence supports their hypothesized structural role in the context of immune stimulation. Here, we showed that these structures in primary macrophages are induced by multiple microbialbased ligands, including exposure to cytosolic double-stranded DNA. Rather than accumulating aggregated proteins, we observed that ubiquitinated proteins form a ring-shaped structure around the perimeter of these circular foci. We identified that different microbial stimuli induced the formation of ubiquitin-positive foci with distinct characteristics and we observed selective recruitment of context-dependent immune regulators. Our findings are consistent with a model where these ubiquitin-containing structures act as adaptable organizing centers for innate immune signaling.SUMMARY Charbonneau et al. demonstrate that ubiquitin- and p62-containing cytosolic ring-shaped structures induced by bacterial infections, microbial ligands and cytosolic double-stranded DNA contain context-dependent immune regulators, revealing an important insight on the cellular architecture required to coordinate signal transduction in macrophage.Competing Interest StatementThe authors have declared no competing interest.ALISaggresome-like induced structures;dsDNAdouble-stranded DNA;iBMDMimmortalized bone-marrow-derived macrophages;LPSlipopolysaccharides;pBMDMprimary bone-marrow-derived macrophages;ROSreactive oxygen species;SMOCsupramolecular organizing centers;TLRToll-like receptors;Ububiquitin. ER -