Role of NKp46+ natural killer cells in house dust mite-driven asthma

House dust mite (HDM)-allergic asthma is driven by T helper 2 (Th2) lymphocytes, but also innate immune cells control key aspects of the disease. The precise function of innate natural killer (NK) cells during the initiation and propagation of asthma has been very confusing, in part because different, not entirely specific, strategies were used to target these cells. We show that HDM inhalation rapidly led to the accumulation of NK cells in the lung-draining lymph nodes and of activated CD69+ NK cells in the bronchoalveolar lumen. However, genetically engineered Ncr1-DTA or Ncr1-DTR mice that constitutively or temporarily lack NK cells, still developed all key features of acute or chronic HDM-driven asthma, such as bronchial hyperreactivity, Th2 cytokine production, eosinophilia, mucus overproduction, and Th2-dependent immunoglobulin serum titers. The same results were obtained by administration of conventional NK1.1 or asialo-GM1 NK cell-depleting antibodies, antibody-mediated blocking of the NKG2D receptor, or genetic NKG2D deficiency. Thus, although NK cells accumulate in allergen-challenged lungs, our findings comprehensively demonstrate that these cells are not required for HDM-driven asthma in the mouse

Intrusion-Tolerant Middleware: the MAFTIA approach

The pervasive interconnection of systems all over the world has given computer services a significant socio-economic value, which can be affected both by accidental faults and by malicious activity. It would be appealing to address both problems in a seamless manner, through a common approach to security and dependability. This is the proposal of intrusion tolerance, where it is assumed that systems remain to some extent faulty and/or vulnerable and subject to attacks that can be successful, the idea being to ensure that the overall system nevertheless remains secure and operational. In this paper, we report some of the advances made in the European project MAFTIA, namely in what concerns a basis of concepts unifying security and dependability, and a modular and versatile architecture, featuring several intrusion-tolerant middleware building blocks. We describe new architectural constructs and algorithmic strategies, such as: the use of trusted components at several levels of abstraction; new randomization techniques; new replica control and access control algorithms. The paper concludes by exemplifying the construction of intrusion-tolerant applications on the MAFTIA middleware, through a transaction support servic

Privacy by Design: From Technologies to Architectures (Position Paper)

Existing work on privacy by design mostly focus on technologies rather than methodologies and on components rather than architectures. In this paper, we advocate the idea that privacy by design should also be addressed at the architectural level and be associated with suitable methodologies. Among other benefits, architectural descriptions enable a more systematic exploration of the design space. In addition, because privacy is intrinsically a complex notion that can be in tension with other requirements, we believe that formal methods should play a key role in this area. After presenting our position, we provide some hints on how our approach can turn into practice based on ongoing work on a privacy by design environment

The transcriptome of lung tumor-infiltrating dendritic cells reveals a tumor-supporting phenotype and a microRNA signature with negative impact on clinical outcome

Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the biology of immune cells in th

MAFTIA Conceptual Model and Architecture

This document builds on the work reported in MAFTIA deliverable D1. It contains a refinement of the MAFTIA conceptual model and a discussion of the MAFTIA architecture. It also introduces the work done in WP6 on verification and assessment of security properties, which is reported on in more detail in MAFTIA deliverable D

Conceptual Model and Architecture of MAFTIA

This deliverable builds on the work reported in [MAFTIA 2000] and [Powell and Stroud 2001]. It contains a further refinement of the MAFTIA conceptual model and a revised discussion of the MAFTIA architecture. It also introduces the work done in MAFTIA on verification and assessment of security properties, which is reported on in more detail in [Adelsbach and Creese 2003

Trust Driven Strategies for Privacy by Design

Part 2: Full PapersInternational audienceIn this paper, we describe a multi-step approach to privacy by design. The main design step is the choice of the types of trust that can be accepted by the stakeholders, which is a key driver for the construction of an acceptable architecture. Architectures can be initially defined in a purely informal way and then mapped into a formal dedicated model. A tool integrating the approach can be used by designers to build and verify architectures. We apply the approach to a case study, an electronic toll pricing system, and show how different solutions can be suggested to the designer depending on different trust assumptions

The lung vascular filter as a site of immune induction for T cell responses to large embolic antigen

The bloodstream is an important route of dissemination of invading pathogens. Most of the small bloodborne pathogens, like bacteria or viruses, are filtered by the spleen or liver sinusoids and presented to the immune system by dendritic cells (DCs) that probe these filters for the presence of foreign antigen (Ag). However, larger pathogens, like helminths or infectious emboli, that exceed 20 µm are mostly trapped in the vasculature of the lung. To determine if Ag trapped here can be presented to cells of the immune system, we used a model of venous embolism of large particulate Ag (in the form of ovalbumin [OVA]-coated Sepharose beads) in the lung vascular bed. We found that large Ags were presented and cross-presented to CD4 and CD8 T cells in the mediastinal lymph nodes (LNs) but not in the spleen or liver-draining LNs. Dividing T cells returned to the lungs, and a short-lived infiltrate consisting of T cells and DCs formed around trapped Ag. This infiltrate was increased when the Toll-like receptor 4 was stimulated and full DC maturation was induced by CD40 triggering. Under these conditions, OVA-specific cytotoxic T lymphocyte responses, as well as humoral immunity, were induced. The T cell response to embolic Ag was severely reduced in mice depleted of CD11chi cells or Ly6C/G+ cells but restored upon adoptive transfer of Ly6Chi monocytes. We conclude that the lung vascular filter represents a largely unexplored site of immune induction that traps large bloodborne Ags for presentation by monocyte-derived DCs