Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response

IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3. This endogenous IgE response, via the IgE receptor FcεRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcεRI in human squamous-cell carcinoma correlated with good disease prognosis. These data indicate a joint role for immunosurveillance by T cells and by B cells in epithelial tissues and suggest that IgE is part of the host defense against epithelial damage and tumor development

An integrated assessment of options for rural wastewater management in Austria

M. Starkl, M. Ornetzeder, E. Binner, P. Holubar, M. Pollak, M. Dorninger, F. Mascher, M. Fuerhacker and R. Haberl;Water Science & Technology, 56 (2007): 5, 105-113This paper reports a recently finished, interdisciplinary project on rural wastewater management in Austria. The objective of the project was to study alternative wastewater management options based on separation of the wastewater into its constituent parts, and to compare them with conventional ones. Thereby, a feasibility study of both conventional and alternative options for wastewater management in six model regions was carried out. Life cycle costs and social acceptance were analysed by using a case study-based assessment approach. However, hygienic and environmental risks were evaluated on a more general level. In order to complement the findings, a survey on urine separation system users in the Solar City of Linz was conducted. Based on these assessments and empirical findings, the paper concludes that options using a full separation of all wastewater fractions should be considered with care. Options based on a separation of only grey water and black water or in the liquid/solid phase can offer ecological and financial advantages over conventional options. Further, options combining wastewater management and regional biogas plants were identified as an interesting solution. However, legal constraints restrict this option currently

Potential of natural treatment technologies for wastewater management in India

High population growth, increasing urbanization and rapid economic development are exerting pressure on the already scarce water resources in India. Treatment and reuse of wastewater can play an important role in addressing some of the urban water challenges. Conventional treatment plants have many challenges, therefore, natural treatment systems (NTSs) are viewed as a cost-effective alternative, which are more suitable in the Indian context. This study builds on a desktop study of NTSs and presents a rapid sustainability assessment of 12 NTSs, highlighting the potential and viability of NTSs in India. The results show that the NTSs have a high potential for wastewater treatment. However, there are still gaps in knowledge related to aspects that hinder the sustainability of the systems. Risks associated with reuse of treated wastewater in agriculture, operational problems and social acceptance were perceived as frequent challenges. Self-sustaining financing methods and the use of by-products were viewed as added benefits

Imaging protective mast cells in living mice during severe contact hypersensitivity

Contact hypersensitivity (CHS) is a common skin disease induced by epicutaneous sensitization to haptens. Conflicting results have been obtained regarding pathogenic versus protective roles of mast cells (MCs) in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. Here we describe a fluorescent imaging approach that enables in vivo selective labeling and tracking of MC secretory granules by real-time intravital 2-photon microscopy in living mice, and permits the identification of such MCs as a potential source of cytokines in different disease models. We show using this method that dermal MCs release their granules progressively into the surrounding microenvironment, but also represent an initial source of the antiinflammatory cytokine IL-10, during the early phase of severe CHS reactions. Finally, using 3 different types of MC-deficient mice, as well as mice in which IL-10 is ablated specifically in MCs, we show that IL-10 production by MCs can significantly limit the inflammation and tissue pathology observed in severe CHS reactions.Laurent L. Reber, Riccardo Sibilano, Philipp Starkl, Axel Roers, Michele A. Grimbaldeston, Mindy Tsai, Nicolas Gaudenzio, and Stephen J. Gall

On classical state space realisability of quadratic input-output differential equations.

This article studies the realisability property of continuous-time quadratic input-output (i/o) equations in the classical state space form. Constraints on the parameters of the quadratic i/o model are suggested that lead to realisable models. The complete list of second- and third-order realisable i/o quadratic models is given and two subclasses of the n-th order realisable i/o quadratic systems are suggested. Our conditions rely basically upon the property that certain combinations of coefficients of the i/o equations are zero or not zero. We provide explicit state equations for realisable second-order quadratic i/o equations, and for one realisable subclass of quadratic i/o equations of arbitrary order

Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide.

Neutrophils have crucial antimicrobial functions but are also thought to contribute to tissue injury upon exposure to bacterial products, such as lipopolysaccharide (LPS). To study the role of neutrophils in LPS-induced endotoxemia, we developed a new mouse model, PMNDTR mice, in which injection of diphtheria toxin induces selective neutrophil ablation. Using this model, we found, surprisingly, that neutrophils serve to protect the host from LPS-induced lethal inflammation. This protective role was observed in conventional and germ-free animal facilities, indicating that it does not depend on a particular microbiological environment. Blockade or genetic deletion of myeloperoxidase (MPO), a key neutrophil enzyme, significantly increased mortality after LPS challenge, and adoptive transfer experiments confirmed that neutrophil-derived MPO contributes importantly to protection from endotoxemia. Our findings imply that, in addition to their well-established antimicrobial properties, neutrophils can contribute to optimal host protection by limiting the extent of endotoxin-induced inflammation in an MPO-dependent manner