Mutations of HFE are associated with hereditary hemochromatosis, but their influence on host susceptibility to infection is incompletely understood. We report that mice lacking one or both Hfe alleles are protected from septicemia with Salmonella Typhimurium, displaying prolonged survival and improved control of bacterial replication. This increased resistance is paralleled by an enhanced production of the enterochelin-binding peptide lipocalin-2 (Lcn2), which reduces the availability of iron for Salmonella within Hfe-deficient macrophages. Accordingly, Hfe−/−Lcn2−/− macrophages are unable to efficiently control the infection or to withhold iron from intracellular Salmonella. Correspondingly, the protection conferred by the Hfe defect is abolished in Hfe−/− mice infected with enterochelin-deficient Salmonella as well as in Hfe−/−Lcn2−/− mice infected with wild-type bacteria. Thus, by induction of the iron-capturing peptide Lcn2, absence of functional Hfe confers host resistance to systemic infection with Salmonella, thereby providing an evolutionary advantage which may account for the high prevalence of genetic hemochromatosis.
Purpose: The aim of this study is to determine the postoperative course after Xen45 Gel Stent implantation at the Medical University of Graz from 2014-2016. Methods: Single-center, retrospective study. All patients with Xen implantation between 2014 and 2016 were included. Clinical records and reports received from supervising ophthalmologists were used for evaluations. Investigated parameters were intraocular pressure (IOP), the number of medications, visual acuity, and the number of previous operations, IOP-follow-up, intraoperative and postoperative complications, the rate of interventions (needling), and additionally performed surgeries. Results: Xen was implanted in 199 eyes of 160 patients. Mean preoperative IOP was 22.8±6.9 mm Hg on 2.9±1.0 IOP-lowering medication. After 12 months follow-up, mean IOP was 17.1±5.9 mm Hg (n=89, P<0.0001; mean reduction of 22.7%) on 1.8±1.4 (n=87; P<0.0001) IOP-lowering medications. There were no intraoperative complications and in two cases (1.0%) severe postoperative adverse events occurred (aqueous misdirection and late-onset endophthalmitis). Postoperative needling was indicated in 44 cases (22.1%), while in 28 cases (14.1%) an additional glaucoma surgery was performed. Conclusions: Our results indicate that Xen implantation is an effective surgical intervention leading to a significant reduction of IOP and number of medications with a low rate of complications. An attentive postoperative management seems to be mandatory.
Lipocalin-2 (Lcn2) is an innate immune peptide with pleiotropic effects. Lcn2 binds iron-laden bacterial siderophores, chemo-attracts neutrophils and has immunomodulatory and apoptosis-regulating effects. In this study we show that upon infection with Salmonella enterica serovar Typhimurium, Lcn2 promotes iron export from Salmonella-infected macrophages, which reduces cellular iron content and enhances the generation of pro-inflammatory cytokines. Lcn2 represses IL-10 production while augmenting Nos2, TNF-α and IL-6 expression. Lcn2-/- macrophages have elevated IL-10 levels as a consequence of increased iron content. The crucial role of Lcn-2/IL-10 interactions was further demonstrated by the greater ability of Lcn2-/- IL-10-/- macrophages and mice to control intracellular Salmonella proliferation in comparison to Lcn2-/- counterparts. Over-expression of the iron exporter ferroportin-1 in Lcn2-/- macrophages represses IL-10 and restores TNF-α and IL-6 production to the levels found in wild-type macrophages, so that killing and clearance of intracellular Salmonella is promoted. Our observations suggest that Lcn2 promotes host resistance to Salmonella Typhimurium infection by binding bacterial siderophores and suppressing IL-10 production, and that both functions are linked to its ability to shuttle iron from macrophages.
Background: The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5∆32 and rheumatoid arthritis (RA) has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA), an association with CCR5 was recently reported. The purpose of this study was to investigate if the CCR5∆32 polymorphism is associated with RA or JIA in Norwegian cohorts.
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