Enhanced Mucosal Antibody Production and Protection against Respiratory Infections Following an Orally Administered Bacterial Extract

Secondary bacterial infections following influenza infection are a pressing problem facing respiratory medicine. Although antibiotic treatment has been highly successful over recent decades, fatalities due to secondary bacterial infections remain one of the leading causes of death associated with influenza. We have assessed whether administration of a bacterial extract alone is sufficient to potentiate immune responses and protect against primary infection with influenza, and secondary infections with either Streptococcus pneumoniae or Klebsiella pneumoniae in mice. We show that oral administration with the bacterial extract, OM-85, leads to a maturation of dendritic cells and B-cells characterized by increases in MHC II, CD86, and CD40, and a reduction in ICOSL. Improved immune responsiveness against influenza virus reduced the threshold of susceptibility to secondary bacterial infections, and thus protected the mice. The protection was associated with enhanced polyclonal B-cell activation and release of antibodies that were effective at neutralizing the virus. Taken together, these data show that oral administration of bacterial extracts provides sufficient mucosal immune stimulation to protect mice against a respiratory tract viral infection and associated sequelae

Systematic Investigations into the Numerical Response Prediction of a Solar Array Stack under Acoustic Excitation

Satellites and payloads launched with large launch vehicles equipped with solid rocket boosters, e.g. ARIANE-5 and NSTS, will be subject to high noise levels during lift-off and atmospheric flight. Particularly sub-systems that have a large surface area and low mass can be very sensitive to acoustic excitation. Examples of such sub-systems are antenna reflectors and solar arrays. This paper presents the main results of a study that follows a systematic approach to investigate the numerical response prediction of a solar array stack, i.e. a solar array in stowed configuration, subject to acoustic excitation. The study has been carried out by Fokker Space (NL) and Metravib R.D.S. (F) under an ESA research and development contract. The hardware selected for the study has been the ARAFOM 5-panel wing. In the frame of the study, the wing has undergone a sequence of mechanical tests, namely a · modal survey test in air and in helium · shaker test with harmonic base excitation (sine test) · acoustic plane wave test · acoustic noise test Results of the modal survey and the sine test, particularly of the modal survey under helium providing a quasi-vacuum environment, have been used to correlate and update the initial mathematical finite element model of the wing. The target of this first step has been to establish a finite element model of the wing that represents as best as possible the dynamic characteristics of the the wing under vacuum conditions. The effects of the air on the dynamic response of the wing have then been modelled by a boundary element approach. This can accurately represent the fluid pressure and radiation impedance loads on the structure. A particular difficulty has been the modelling of the thin air gaps in between the individual panels of the wing. Responses of the wing to acoustic plane wave excitation have been computed and have been correlated with the responses measured from the acoustic plane wave testResponses have been evaluated in terms of structural accelerations and stresses, but also in terms of acoustic pressures in the inter panel gaps and the surrounding fluid. Eventually, the response of the wing to acoustic noise excitation has been numerically simulated using a superposition of plane acoustic waves, and the results have been correlated with the responses from the acoustic noise test

Engineering access to higher education through higher education fairs

Text from van Zanten A., Legavre A. “Engineering access to higher education through higher education fairs”, in Goastellec G., Picard F. (ed.) The Roles of Higher Education and Research in the Fabric of Societies, Leuven, Sense Publishers, 2014 (in press). Transition to higher education is a major social process. This transition has been mostly studied by French sociologists of education and higher education from perspectives focusing predominantly on the role of the socio-economic status, academic profiles and different tracks followed by secondary school students (Merle 1996, Duru-Bellat and Kieffer 2008, Convert 2010), and, to a lesser extent, on the types of secondary schools attended (Duru-Bellat and Mingat 1998, Nakhili 2005) and the local higher education provision (Berthet et al. 2010, Orange 2013). Although these structural determinants play a major role in explaining significant regularities, they provide more powerful explanations for individuals representing the extremes of the different variables considered, leaving room for the influence of other major factors for those students in intermediate situations. In addition, even in the case of students occupying extreme positions, structural perspectives better explain the distribution of students between different higher education tracks than they do between institutions and disciplines. In this chapter, we adopt a perspective that we see as complementary to and interacting with the perspective centred on structural determinants by focusing on the role of the devices that mediate the exchanges between students and higher education institutions, and more specifically on one device: higher education fairs. Our purpose in doing so is not only to document how these various devices frame, in ways that remain largely unexplored by researchers, exchanges between providers and consumers of higher education but also to point out – and further explore in future publications – how these devices, and the specific features of fairs, contribute to the reproduction and transformation of educational inequalities in access to higher education (Benninghoff et al. 2012)

Defining an olfactory receptor function in airway smooth muscle cells

Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (G olf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells. In a heterologous expression system, OR51E2 trafficked readily to the cell surface and showed ligand selectivity and sensitivity to the short chain fatty acids (SCFAs) acetate and propionate. These endogenous metabolic byproducts of the gut microbiota slowed the rate of cytoskeletal remodeling, as well as the proliferation of human ASM cells. These cellular responses in vitro were found in ASM from non-asthmatics and asthmatics, and were absent in OR51E2-deleted primary human ASM. These results demonstrate a novel chemo-mechanical signaling network in the ASM and serve as a proof-of-concept that a specific receptor of the gut-lung axis can be targeted to treat airflow obstruction in asthma.open0

Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers

Pattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury, or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4)-mediated sterile inflammation. Here we map three sites within tenascin-C that directly and cooperatively interact with TLR4. We also identify a conserved inflammatory epitope in related proteins from diverse families, and demonstrate that its presence targets molecules for TLR detection, while its absence enables escape of innate immune surveillance. These data reveal a unique molecular code that defines endogenous proteins as inflammatory stimuli by marking them for recognition by TLRs

TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways

Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases. Moreover, inhaled endotoxin may play an important role in the development and progression of airway inflammation in asthma. Pathologic changes induced by endotoxin inhalation include bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of the alveolar epithelium, and disruption of pulmonary capillary integrity leading to protein rich fluid leak in the alveolar space. Mammalian Toll-like receptors (TLRs) are important signalling receptors in innate host defense. Among these receptors, TLR4 plays a critical role in the response to endotoxin

Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation

Resident intravascular NKT cells exacerbate airway hyperreactivity in mice dependent on dendritic cell co-presentation of glycolipid and peptide antigens

Targeting IL-1β and IL-17A driven inflammation during influenza-induced exacerbations of chronic lung inflammation.

For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are key mediators of neutrophilic inflammation in influenza-induced exacerbations of chronic lung inflammation. Using a mouse model of disease, our data shows a role for IL-1β in mediating lung dysfunction, and in driving neutrophilic inflammation during the whole phase of viral infection. We further report a role for IL-17A as a mediator of IL-1β induced neutrophilia at early time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1 resulted in a significant abrogation of neutrophil recruitment to the airways in the initial phase of infection or at the peak of viral replication, respectively. Therefore, IL-17A and IL-1β are potential targets for therapeutic treatment of viral exacerbations of chronic lung inflammation