The high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a clinical threat; diverse genetic mechanisms (strains/plasmids/insertion sequences) have contributed to the dissemination of mcr-1, and will facilitate its persistence.

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B-cell biology has been largely uncharacterized in the field of tuberculosis (TB). In this study, we investigated the immunophenotypical and functional characteristics of B cells obtained from the pleural fluid (PF) and peripheral blood of patients with tuberculous pleuritis (TP). Our results indicated that the total numbers of B cells, CD271 memory B cells and plasmablasts were clearly lower in the PF than in peripheral blood. Furthermore, we found significantly higher expression of CXCR4 on B cells in the PF, and a chemotaxis assay showed that B cells in the PF were more responsive to stromal cell-derived factor-1 (SDF-1) than B cells from peripheral blood. In addition, SDF-1 levels in PF were remarkably high compared with SDF-1 levels in plasma, suggesting that the SDF-1/CXCR4 axis might facilitate the migration of circulating B cells into tuberculous pleural space. Importantly, we observed that significantly more antibodies were produced by B cells in the PF following stimulation with BCG, early secretory antigenic target (ESAT-6)/culture filtrate protein-10 (CFP-10) or ESAT-6 protein.Collectively, these data demonstrate that Mycobacterium tuberculosis-specific B cells exist at local sites of infection in TP patients and this localization might influence the immune response to M. tuberculosis. Key words: B cells . Chemokine receptors . Immune responses . Tuberculous pleuritis Supporting Information available onlineIntroduction Tuberculosis (TB), one of the oldest infectious diseases associated with humans, is a chronic disease caused by infection with Mycobacterium tuberculosis [1,2]. The incidence of TB has increased during the past 20 years for reasons such as insufficient prevention efforts, incorrectly prescribed medication, the emergence of drug-resistant strains of M. tuberculosis and the prevalence of human immunodeficiency virus (HIV) infection [3,4]. Traditionally, the immune response against M. tuberculosis infection is dominated by cell-mediated immunity (CMI), which relies primarily on CD4 1 and CD8 1 T cells. Therefore, many studies have been conducted in an attempt to augment cellular immunity, with an aim to develop new vaccine candidates against TB [5][6][7]. In contrast to these investigations, the contribution of B cells and humoral immunity in the TB field remains largely unexamined and elusive. Fewer efforts to promote an effective humoral response against M. tuberculosis have been made compared with those devised to elicit a cellular response [8]. However, it is worth noting that any successful, novel vaccine strategy against TB will have to properly invoke both humoral and cellular immunity, given that these responses are the two critical arms of adaptive immunity and always collaborate to repel infectious pathogens [9]. Numerous murine studies have shown that B cells and antibodies have pleiotropic activities and display previously underappreciated roles during M. tuberculosis infection [10][11][12]. In contrast to the murine studies, there are limited data regarding any phenotypic and...

Background: Gut microbiota has a number of essential roles in nutrition metabolism and immune homeostasis, and is closely related to hepatocellular progression. In recent years, studies have also shown that FK506 binding protein 5 (FKBP-5) plays a crucial role in immune regulation. However, it is not yet clear whether FKBP-5 promotes the development of hepatocellular carcinoma (HCC) by affecting immune function and gut microbiota.Methods: FKBP-5 expression was verified by immunochemistry and western blot and reverse transcription polymerase chain reaction (RT-qPCR) assays. After treatment in WT and FKBP-5 -/mice, the histological characteristic of mice liver tissue was assessed by H&E staining, and hepatic leukocytes and hepatic NKT cells were identified by flow cytometer. Meanwhile, primary bile acids (BAs), secondary BAs, serum total cholesterol, and the weight of abdomen adipose tissues were examined, and the gut microbiota was evaluated by 16S ribosomal ribonucleic acid (rRNA) sequencing.Results: We discovered that FKBP-5 was highly expressed in HCC tissues. Meanwhile, FKBP-5 deletion inhibited tumor progression by increasing CD 8+ T, CD 4+ T, NKT and CD 4+ NKT cells in mice after diethylnitrosamine (DEN) injection. Besides, we proved that FKBP-5 deletion generated rapid and significant reductions in the intestinal BAs, the weight of abdomen adipose tissues and the serum total cholesterol. FKBP-5 deletion also led to a change in the composition of gut microbiota, suggesting that BAs are the main dietary factor regulating gut microbiota, which could be affected by FKBP-5 deletion. Further, we uncovered that anti-CD4 and anti-CD8 treatments facilitated hepatocellular progression by modulating gut microbiota composition in FKBP-5 -/mice.Conclusions: Therefore, we demonstrated that FKBP-5 deletion inhibited hepatocellular progression by modulating immune response and gut microbiome-mediated BAs metabolism.