Epstein-Barr Virus Infection Is Associated with Elevated Hepcidin Levels.

EBV and Helicobacter pylori (H. pylori) cause highly prevalent persistent infections as early as in childhood. Both pathogens are associated with gastric carcinogenesis. H. pylori interferes with iron metabolism, enhancing the synthesis of acute-phase proteins hepcidin, C-reactive protein (CRP), and α-1 glycoprotein (AGP), but we do not know whether EBV does the same. In this study, we correlated the EBV antibody levels and the serum levels of hepcidin, CRP, and AGP in 145 children from boarding schools in Mexico City. We found that children IgG positive to EBV antigens (VCA, EBNA1, and EA) presented hepcidin, AGP, and CRP levels higher than uninfected children. Hepcidin and AGP remained high in children solely infected with EBV, while CRP was only significantly high in coinfected children. We observed positive correlations between hepcidin and EBV IgG antibodies (p < 0.5). Using the TCGA gastric cancer database, we also observed an association between EBV and hepcidin upregulation. The TCGA database also allowed us to analyze the two important pathways controlling hepcidin expression, BMP−SMAD and IL-1ß/IL-6. We observed only the IL-1ß/IL-6-dependent inflammatory pathway being significantly associated with EBV infection. We showed here for the first time an association between EBV and enhanced levels of hepcidin. Further studies should consider EBV when evaluating iron metabolism and anemia, and whether in the long run this is an important mechanism of undernourishment and EBV gastric carcinogenesis.

Prolactin Rescues Immature B Cells from Apoptosis-Induced BCR-Aggregation through STAT3, Bcl2a1a, Bcl2l2, and Birc5 in Lupus-Prone MRL/lpr Mice.

Self-reactive immature B cells are eliminated through apoptosis by tolerance mechanisms, failing to eliminate these cells results in autoimmune diseases. Prolactin is known to rescue immature B cells from B cell receptor engagement-induced apoptosis in lupus-prone mice. The objective of this study was to characterize in vitro prolactin signaling in immature B cells, using sorting, PCR array, RT-PCR, flow cytometry, and chromatin immunoprecipitation. We found that all B cell maturation stages in bone marrow express the prolactin receptor long isoform, in both wild-type and MRL/lpr mice, but its expression increased only in the immature B cells of the latter, particularly at the onset of lupus. In these cells, activation of the prolactin receptor promoted STAT3 phosphorylation and upregulation of the antiapoptotic Bcl2a1a, Bcl2l2, and Birc5 genes. STAT3 binding to the promoter region of these genes was confirmed through chromatin immunoprecipitation. Furthermore, inhibitors of prolactin signaling and STAT3 activation abolished the prolactin rescue of self-engaged MRL/lpr immature B cells. These results support a mechanism in which prolactin participates in the emergence of lupus through the rescue of self-reactive immature B cell clones from central tolerance clonal deletion through the activation of STAT3 and transcriptional regulation of a complex network of genes related to apoptosis resistance.

Pyrosequencing analysis of the bacterial community in drinking water wells.

Wells used for drinking water often have a large biomass and a high bacterial diversity. Current technologies are not always able to reduce the bacterial population, and the threat of pathogen proliferation in drinking water sources is omnipresent. The environmental conditions that shape the microbial communities in drinking water sources have to be elucidated, so that pathogen proliferation can be foreseen. In this work, the bacterial community in nine water wells of a groundwater aquifer in Northern Mexico were characterized and correlated to environmental characteristics that might control them. Although a large variation was observed between the water samples, temperature and iron concentration were the characteristics that affected the bacterial community structure and composition in groundwater wells. Small increases in the concentration of iron in water modified the bacterial communities and promoted the growth of the iron-oxidizing bacteria Acidovorax. The abundance of the genera Flavobacterium and Duganella was correlated positively with temperature and the Acidobacteria Gp4 and Gp1, and the genus Acidovorax with iron concentrations in the well water. Large percentages of Flavobacterium and Pseudomonas bacteria were found, and this is of special concern as bacteria belonging to both genera are often biofilm developers, where pathogens survival increases.