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Early life represents a major risk window for asthma development. However, the mechanisms controlling the threshold for establishment of allergic airway inflammation in early life are incompletely understood. Airway macrophages (AMs) regulate pulmonary allergic responses and undergo TGF-β–dependent postnatal development, but the role of AM maturation factors such as TGF-β in controlling the threshold for pathogenic immune responses to inhaled allergens remains unclear. Our aim was to test the hypothesis that AM-derived TGF-β1 regulates pathogenic immunity to inhaled allergen in early life. Conditional knockout (Tgfb1 ΔCD11c) mice, with TGF-β1 deficiency in AMs and other CD11c+ cells, were analyzed throughout early life and following neonatal house dust mite (HDM) inhalation. The roles of specific chemokine receptors were determined by using in vivo blocking antibodies. AM-intrinsic TGF-β1 was redundant for initial population of the neonatal lung with AMs, but AMs from Tgfb1 ΔCD11c mice failed to adopt a mature homeostatic AM phenotype in the first weeks of life. Evidence of constitutive TGF-β1 signaling was also observed in pediatric human AMs. TGF-β1–deficient AMs expressed enhanced levels of monocyte-attractant chemokines, and accordingly, Tgfb1 ΔCD11c mice exposed to HDM throughout early life accumulated CCR2-dependent inflammatory CD11c+ mononuclear phagocytes into the airway niche that expressed the proallergic chemokine CCL8. Tgfb1 ΔCD11c mice displayed augmented T H 2, group 2 innate lymphoid cell, and airway remodeling responses to HDM, which were ameliorated by blockade of the CCL8 receptor CCR8. Our results highlight a causal relationship between AM maturity, chemokines, and pathogenic immunity to environmental stimuli in early life and identify TGF-β1 as a key regulator of this. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: In Fiji, economic valuation has not yet been adopted as an aid to coastal resource management. Given increasing pressures on its coastal resources, particularly near urban centres, valuation of these resources may be crucial to assist decision-making at all levels. This paper presents estimates of the economic value of the main goods and services provided by the coastal ecosystems in a traditional Fijian fishing ground near the capital, Suva. Using catch surveys, a CV survey and secondary data sources, the value of fisheries, bequest value and coastal protection function provided by the coral reefs and mangroves within this area are estimated to provide net benefits of just over FJ$3m (US$1,795,000) per year. The coastal protection provided by the coral reefs and mangroves makes up the largest component of the total economic value (55%) followed by fisheries (44%). Bequest values only make up 1% of the TEV. However, if compared to household income, bequest values are significant, representing 6.8% of stated income. This is comparable to average expenditures on durable household goods and heating and lighting. [Copyright &y& Elsevier]

Abstract: Regulatory T cells (TReg) control immune responses to self and nonself Ags. The relationship between Ag-driven IL-10-secreting TReg (IL-10-TReg) and naturally occurring CD4 CD25 TReg is as yet unclear. We show that mouse IL-10-TReg obtained using either in vitro or in vivo regimens of antigenic stimulation did not express the CD4 CD25 TReg-associated transcription factor Foxp3. However, despite the absence of Foxp3 expression, homogeneous populations of IL-10-TReg inhibited the in vitro proliferation of CD4 CD25 T cells with a similar efficiency to that of CD4 CD25 TReg. This inhibition of T cell proliferation by IL-10-TReg was achieved through an IL-10-independent mechanism as seen for CD4 CD25 TReg and was overcome by exogenous IL-2. Both IL-10-TReg and CD4 CD25 TReg were similar in that they produced little to no IL-2. These data show that Foxp3 expression is not a prerequisite for IL-10-TReg activity in vitro or in vivo and suggest that IL-10-TReg and naturally occurring CD4 CD25 TReg may have distinct origins. Thus, these different regulatory populations may have different roles at different stages of the immune response. [Copyright &y& Elsevier]

Abstract: This paper investigates the determinants of knowledge and acceptability of hydrogen vehicles among London residents. Data was collected via a socio-economic survey of over four hundred residents. Results indicate that, at present, less than half of respondents have heard of hydrogen as a fuel for transport, and just over one-third are clearly in favour of the introduction of hydrogen vehicles. The key determinant of acceptability was having prior awareness of hydrogen technologies, as identified via logit regression analysis. Hydrogen awareness in turn was found to be related to gender, age, education and environmental knowledge. These results suggest that there is an opportunity to raise awareness of hydrogen technologies among the remaining three-fifths of the London population, although this is likely to require a differential approach to information provision. [Copyright &y& Elsevier]

A finite element model called MasSET has been developed which is capable of predicting the structural behaviour of single leaf masonry walls subject to elevated temperatures. The analysis models a slice through the wall as a column strip in plane stress, and also includes material with geometric non-linearity. The model has been previously validated by comparison with experimental results and is used in this paper to conduct a parametric study investigating the effects of slenderness ratio, load eccentricity and boundary conditions. The results of the investigation are presented by way of failure temperatures for each condition, and show conclusive findings to the effects of each parameter investigated. [Copyright &y& Elsevier]

Intricate immune regulation is required at mucosal surfaces to allow tolerance to microbiota and harmless allergens and to prevent overexuberant inflammatory responses to pathogens. The cytokine Interleukin-10 (IL-10) is a key mediator of mucosal immune regulation. While IL-10 can be produced by virtually all cells of the immune system, many of its in vivo functions depend upon its production by regulatory or effector T cell populations and its signalling to macrophages, dendritic cells and specific T cell subsets. In this review, we discuss our current understanding of the role of IL-10 in regulation of immune responses, with a focus on its context-specific roles in intestinal homeostasis, respiratory infection and asthma. We highlight the importance of appropriate production and function of IL-10 for balancing pathogen clearance, control of microbiota and host tissue damage, and that precise modulation of IL-10 functions in vivo could present therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Although originally defined as a type 2 (T2) immune-mediated condition, non-T2 cytokines, such as IFN-γ and IL-17A, have been implicated in asthma pathogenesis, particularly in patients with severe disease. IL-10 regulates T H cell phenotypes and can dampen T2 immunity to allergens, but its functions in controlling non-T2 cytokine responses in asthmatic patients are unclear. We sought to determine how IL-10 regulates the balance of T H cell responses to inhaled allergen. Allergic airway disease was induced in wild-type, IL-10 reporter, and conditional IL-10 or IL-10 receptor α (IL-10Rα) knockout mice by means of repeated intranasal administration of house dust mite (HDM). IL-10 and IFN-γ signaling were disrupted by using blocking antibodies. Repeated HDM inhalation induced a mixed IL-13/IL-17A response and accumulation of IL-10–producing forkhead box P3–negative effector CD4+ T cells in the lungs. Ablation of T cell–derived IL-10 increased the IFN-γ and IL-17A response to HDM, reducing IL-13 levels and airway eosinophilia without affecting IgE levels or airway hyperresponsiveness. The increased IFN-γ response could be recapitulated by IL-10Rα deletion in CD11c+ myeloid cells or local IL-10Rα blockade. Disruption of the T cell–myeloid IL-10 axis resulted in increased pulmonary monocyte–derived dendritic cell numbers and increased IFN-γ–dependent expression of CXCR3 ligands by airway macrophages, which is suggestive of a feedforward loop of T H 1 cell recruitment. Augmented IFN-γ responses in the HDM allergic airway disease model were accompanied by increased disruption of airway epithelium, which was reversed by therapeutic blockade of IFN-γ. IL-10 from effector T cells signals to CD11c+ myeloid cells to suppress an atypical and pathogenic IFN-γ response to inhaled HDM. [ABSTRACT FROM AUTHOR]

• Quantitative changes in QuantiFERON-TB Gold (QFT) response do not stratify tuberculosis (TB) risk in QFT-positive contacts. • QFT conversion after 3 months identifies contacts at significantly increased TB risk. • QFT conversion is associated with exposure to rapidly progressive pulmonary TB. • Pre-existing latent TB infection may protect against developing TB following re-exposure. We investigated whether quantifying the serial QuantiFERON-TB Gold (QFT) response improves tuberculosis (TB) risk stratification in pulmonary TB (PTB) contacts. A total of 297 untreated adult household PTB contacts, QFT tested at baseline and 3 months after index notification, were prospectively observed (median 1460 days). Normal variance of serial QFT responses was established in 46 extrapulmonary TB contacts. This informed categorisation of the response in QFT-positive PTB contacts as converters, persistently QFT-positive with significant increase (PP increase), and without significant increase (PP no-increase). In total, eight co-prevalent TB (disease ≤3 months after index notification) and 12 incident TB (>3 months after index notification) cases were diagnosed. Genetic linkage to the index strain was confirmed in all culture-positive progressors. The cumulative 2-year incident TB risk in QFT-positive contacts was 8.4% (95% confidence interval, 3.0-13.6%); stratifying by serial QFT response, significantly higher risk was observed in QFT converters (28%), compared with PP no-increase (4.8%) and PP increase (3.7%). Converters were characterised by exposure to index cases with a shorter interval from symptom onset to diagnosis (median reduction 50.0 days, P = 0.013). QFT conversion, rather than quantitative changes of a persistently positive serial QFT response, is associated with greater TB risk and exposure to rapidly progressive TB. [ABSTRACT FROM AUTHOR]

Highlights: [•] Blood transcriptional profiling in human TB has been reproducible in many studies. [•] Transcriptional profiling has highlighted the importance of type I interferons in TB. [•] Transcriptional profiles provide biomarkers for diagnosis and treatment monitoring. [ABSTRACT FROM AUTHOR]

Neutrophils are rapidly recruited to sites of mycobacterial infection, where they phagocytose bacilli. Whether neutrophils can kill mycobacteria in vivo probably depends on the tissue microenvironment, stage of infection, individual host, and infecting organism. The interaction of neutrophils with macrophages, as well as the downstream effects on T cell activity, could result in a range of outcomes from early clearance of infection to dissemination of viable bacteria together with an attenuated acquired immune response. In established disease, neutrophils accumulate in situations of high pathogen load or immunological dysfunction, and are likely to contribute to pathology. These activities may have clinical importance in terms of new treatments, targeted interventions and vaccine strategies. [ABSTRACT FROM AUTHOR]

The tripartite motif containing (TRIM) proteins are a family of proteins that have been implicated in many biological processes including cell differentiation, apoptosis, transcriptional regulation and signaling pathways. Many TRIM proteins are upregulated by the immunologically important Type I and Type II interferons and several, including TRIM5α and TRIM19/PML, restrict viral replication. There is growing evidence that TRIMs also play an important role in the broader immune response through regulating signaling pathways such as the RIG-I pathway. In this review we discuss recent research elucidating TRIM regulation of a number of pathways important in immunity and review the latest findings relating to viral restriction by TRIMs. [Copyright &y& Elsevier]