Percorrer por autor "Vilanova, Manuel"
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- Involvement of the Iron-Regulated Loci hts and fhuC in Biofilm Formation and Survival of Staphylococcus epidermidis within the HostPublication . Oliveira, Fernando; Lima, Tânia; Correia, Alexandra; Silva, Ana Margarida; Soares, Cristina; Morais, Simone; Weißelberg, Samira; Vilanova, Manuel; Rohde, Holger; Cerca, NunoStaphylococcus epidermidis is a major nosocomial pathogen with a remarkable ability to persist on indwelling medical devices through biofilm formation. Nevertheless, it remains intriguing how this process is efficiently achieved under the host’s harsh conditions, where the availability of nutrients, such as essential metals, is scarce. Following our previous identification of two iron-regulated loci putatively involved in iron transport, hts and fhuC, we assessed here their individual contribution to both bacterial physiology and interaction with host immune cells. Single deletions of the hts and fhuC loci led to marked changes in the cell iron content, which were partly detrimental for planktonic growth and strongly affected biofilm formation under iron-restricted conditions. Deletion of each of these two loci did not lead to major changes in S. epidermidis survival within human macrophages or in an ex vivo human blood model of bloodstream infection. However, the lack of either hts or fhuC loci significantly impaired bacterial survival in vivo in a murine model of bacteremia. Collectively, this study establishes, for the first time, the pivotal role of the iron-regulated loci hts and fhuC in S. epidermidis biofilm formation and survival within the host, providing relevant information for the development of new targeted therapeutics against this pathogen
- Metabolic control of T cell immune response through glycans in inflammatory bowel diseasePublication . Dias, Ana M.; Correia, Alexandra; Pereira, Márcia S.; Almeida, Catarina R.; Alves, Inês; Pinto, Vanda; Catarino, Telmo A.; Mendes, Nuno; Leander, Magdalena; Oliva-Teles, MT; Maia, Luís; Delerue-Matos, Cristina; Taniguchi, Naoyuki; Lima, Margarida; Pedroto, Isabel; Marcos-Pinto, Ricardo; Lago, Paula; Reis, Celso A.; Vilanova, Manuel; Pinho, Salomé S.Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5−/−, MGAT5+/−) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.