Clostridium perfringens α-toxin impairs granulocyte colony-stimulating factor receptor-mediated granulocyte production while triggering septic shock.

During bacterial infection, granulocyte colony-stimulating factor (G-CSF) is produced and accelerates neutrophil production from their progenitors. This process, termed granulopoiesis, strengthens host defense, but Clostridium perfringens α-toxin impairs granulopoiesis via an unknown mechanism. Here, we tested whether G-CSF accounts for the α-toxin-mediated impairment of granulopoiesis. We find that α-toxin dramatically accelerates G-CSF production from endothelial cells in response to Toll-like receptor 2 (TLR2) agonists through activation of the c-Jun N-terminal kinase (JNK) signaling pathway. Meanwhile, α-toxin inhibits G-CSF-mediated cell proliferation of Ly-6G+ neutrophils by inducing degradation of G-CSF receptor (G-CSFR). During sepsis, administration of α-toxin promotes lethality and tissue injury accompanied by accelerated production of inflammatory cytokines in a TLR4-dependent manner. Together, our results illustrate that α-toxin disturbs G-CSF-mediated granulopoiesis by reducing the expression of G-CSFR on neutrophils while augmenting septic shock due to excess inflammatory cytokine release, which provides a new mechanism to explain how pathogenic bacteria modulate the host immune system.

Cesium Uptake by Rice Roots Largely Depends Upon a Single Gene, HAK1, Which Encodes a Potassium Transporter.

Incidents at the Fukushima and Chernobyl nuclear power stations have resulted in widespread environmental contamination by radioactive nuclides. Among them, 137cesium has a 30 year half-life, and its persistence in soil raises serious food security issues. It is therefore important to prevent plants, especially crop plants, from absorbing radiocesium. In Arabidopsis thaliana, cesium ions are transported into root cells by several different potassium transporters such as high-affinity K+ transporter 5 (AtHAK5). Therefore, the cesium uptake pathway is thought to be highly redundant, making it difficult to develop plants with low cesium uptake. Here, we isolated rice mutants with low cesium uptake and reveal that the Oryza sativa potassium transporter OsHAK1, which is expressed on the surfaces of roots, is the main route of cesium influx into rice plants, especially in low potassium conditions. During hydroponic cultivation with low to normal potassium concentrations (0-206 µM: the normal potassium level in soil), cesium influx in OsHAK1-knockout lines was no greater than one-eighth that in the wild type. In field experiments, knockout lines of O. sativa HAK1 (OsHAK1) showed dramatically reduced cesium concentrations in grains and shoots, but their potassium uptake was not greatly affected and their grain yields were similar to that of the wild type. Our results demonstrate that, in rice roots, potassium transport systems other than OsHAK1 make little or no contribution to cesium uptake. These results show that low cesium uptake rice lines can be developed for cultivation in radiocesium-contaminated areas.

The Use of an Enzyme-based Sensor Array to Fingerprint Proteomic Signatures of Sera from Different Mammalian Species.

A cross-reactive sensor array consisting of polyion complexes (PICs) between anionic enzymes and poly(ethylene glycol)-modified (PEGylated) polyamines has been used to identify the source of mammalian sera. Although the catalytic activity of enzymes was inhibited by PIC formation with PEGylated polyamines, the subsequent addition of sera caused enzyme releases from PICs through competitive interactions between PICs and serum proteins, generating unique response patterns of changes in the enzyme activity. Linear discriminant analysis of the obtained patterns enabled the discrimination of five sera from different mammalian sources.