Pairing Bacteroides vulgatus LPS structure with its immunomodulatory effects on human cellular models

15 p.-5 fig.-1 tab.-1 graph abst. This paper is dedicated to Prof. Jesús Jiménez-Barbero for his 60th birthday.The gut microbiota guide the development of the host immune system by setting a systemic threshold for immune activation. Lipopolysaccharides (LPSs) from gut bacteria are able to trigger systemic and local proinflammatory and immunomodulatory responses, and this capability strongly relies on their fine structures. Up to now, only a few LPS structures from gut commensals have been elucidated; therefore, the molecular motifs that may be important for LPS–mammalian cell interactions at the gut level are still obscure. Here, we report on the full structure of the LPS isolated from one of the prominent species of the genus Bacteroides, Bacteroides vulgatus. The LPS turned out to consist of a particular chemical structure based on hypoacylated and mono-phosphorylated lipid A and with a galactofuranose-containing core oligosaccharide and an O-antigen built up of mannose and rhamnose. The evaluation of the immunological properties of this LPS on human in vitro models revealed a very interesting capability to produce anti-inflammatory cytokines and to induce a synergistic action of MD-2/TLR4- and TLR2-mediated signaling pathways.F.D.L. acknowledges Progetto STAR 2018 Linea 1 grant E66C18001330003. S.M.S. acknowledges Spanish Ministry of Science (ref. CTQ2017-88353-R). A.M., F.D.L., and A.S.acknowledge H2020 Marie Skłodowska-Curie ITN 2018 “SweetCrossTalk” grant 814102. A.M. acknowledges progetto POR SATIN POR-FESR 2014−2 0 2 0 g r a n t B61C17000070007 (OR3) and Progetto POR Campania Oncoterapia 2014−2020 grant B61G18000470007. A.S. acknowledges PRIN-MIUR 2017 Glytunes project. A.S. and F.C. acknowledge COST (European Cooperation in Science and Technology) Action CA18103 (INNOGLY). F.C. was financially supported by the NWO Spinoza award of Y.K.Peer reviewe

Patient's dermal fibrolasts as disease markers for visceral myopathy

Visceral myopathy (VSCM) is a rare genetic disease, orphan of pharmacological therapy. VSCM diagnosis is not always straightforward due to symptomatology similarities with mitochondrial or neuronal forms of intestinal pseudo-obstruction. The most prevalent form of VSCM is associates with variants in the gene ACTG2, encoding the protein gamma-2 actin. Overall, VSCM is a mechano-biological disorder, in which different genetic variants lead to similar alterations to the contractile phenotype of enteric smooth muscles, resulting in the emergence of life-threatening symptoms. In this work we analyzed the morpho-mechanical phenotype of human dermal fibroblasts from patients affected with VSCM, demonstrating that they retain a clear signature of the disease when compared with different controls. We evaluated several biophysical traits of fibroblasts, and we show that a measure of cellular traction forces can be used as a non-specific biomarker of the disease. We propose that a simple assay based on traction forces could be designed to provide a valuable support for clinical decision or pre-clinical research