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Helminths regulate host immune responses to ensure their own long-term survival. Numerous studies have demonstrated that these helminth-induced regulatory mechanisms can also limit host inflammatory responses in several disease models. We used the Heligmosomoides bakeri (Hb) infection model (also known as H. polygyrus or H. polygyrus bakeri in the literature) to test whether such immune regulation affects skin inflammatory responses induced by the model contact sensitiser dibutyl phthalate fluorescein isothiocynate (DBP-FITC). Skin lysates from DBP-FITC-sensitized, Hb-infected mice produced less neutrophil specific chemokines and had significantly reduced levels of skin thickening and cellular inflammatory responses in tissue and draining lymph nodes (LNs) compared to uninfected mice. Hb-induced suppression did not appear to be mediated by regulatory T cells, nor was it due to impaired dendritic cell (DC) activity. Mice cleared of infection remained unresponsive to DBP-FITC sensitization indicating that suppression was not via the secretion of Hb-derived short-lived regulatory molecules, although long-term effects on cells cannot be ruled out. Importantly, similar helminth-induced suppression of inflammation was also seen in the draining LN after intradermal injection of the ubiquitous allergen house dust mite (HDM). These findings demonstrate that Hb infection attenuates skin inflammatory responses by suppressing chemokine production and recruitment of innate cells. These findings further contribute to the growing body of evidence that helminth infection can modulate inflammatory and allergic responses via a number of mechanisms with potential to be exploited in therapeutic and preventative strategies in the future.

Basophils are granulocytes involved in parasite immunity and allergic diseases, known for their potent secretion of type 2 cytokines. Identifying their functions has proven to be controversial due to their relative rarity and their complex lineage phenotype. Here, we show that the expression of basophils lineage markers CD200R3 and FcεRIα is highly variable in inflammatory settings and hinders basophils identification by flow cytometry across multiple disease states or tissues. Fluorophore-conjugated antibody staining of these lineage markers strongly activates basophil type 2 cytokine expression, and represents a potential bias for coculture or in vivo transfer experiments. The Basoph8 is a mouse model where basophils specifically express a strong fluorescent reporter and the Cre recombinase. Basophils can be identified and FACS sorted unambiguously by their expression of the enhanced yellow fluorescent protein (eYFP) in these mice. We show that the expression of the eYFP is robust in vivo during inflammation, and in vitro on living basophils for at least 72 h, including during the induction of anaphylactoid degranulation. We bred and characterized the Basoph8xiDTR mice, in which basophils specifically express eYFP and the simian diphtheria toxin receptor (DTR). This model enables basophils conditional depletion relatively specifically ex vivo and in vivo during allergic inflammation and their detection as eYFP+ cells. In conclusion, we report underappreciated benefits of the commercially available Basoph8 mice to study basophils function.

Group 2 innate lymphoid cells (ILC2s) were first discovered in experimental studies of intestinal helminth infection—and much of our current knowledge of ILC2 activation and function is based on the use of these models. It is perhaps not surprising therefore that these cells have also been found to play a key role in mediating protection against these large multicellular parasites. ILC2s have been intensively studied over the last decade, and are known to respond quickly and robustly to the presence of helminths—both by increasing in number and producing type 2 cytokines. These mediators function to activate and repair epithelial barriers, to recruit other innate cells such as eosinophils, and to help activate T helper 2 cells. More recent investigations have focused on the mechanisms by which the host senses helminth parasites to activate ILC2s. Such studies have identified novel stromal cell types as being involved in this process—including intestinal tuft cells and enteric neurons, which respond to the presence of helminths and activate ILC2s by producing IL-25 and Neuromedin, respectively. In the current review, we will outline the latest insights into ILC2 activation and discuss the requirement for—or redundancy of—ILC2s in providing protective immunity against intestinal helminth parasites.

Although IL-4 is long associated with CD4 Th2 immune responses, its role in Th2 subset development in non-lymphoid tissues is less clear. We sought to better define IL-4’s role in CD4 Th2 responses by using transgenic mice that express a dual IL-4 AmCyan/IL-13 DsRed (IL-4AC/IL-13DR) fluorescent reporter on an IL-4-sufficient or IL-4-deficient background. Using primary Th2 immune response models against house dust mite or Nippostrongylus brasiliensis (Nb) allergens, we examined the requirement for IL-4 by each of the defined Th2 subsets in the antigen draining lymph node, skin, and lung tissues. In the lymph node, a CXCR5+PD-1+ T follicular helper (Tfh) and a CXCR5loPD-1lo Th2 subset could be detected that expressed only IL-4AC but no IL-13DR. The number of IL-4AC+ Tfh cells was not affected by IL-4 deficiency whereas the number of IL-4AC+ Th2 cells was significantly reduced. In the non-lymphoid dermal or lung tissues of allergen primed or Nb-infected mice, three strikingly distinct T cell subsets could be detected that were IL-4AC, or IL-4AC/IL-13DR, or IL-13DR CD4. The IL-4- and IL-4/IL-13-expressing subsets were significantly reduced in IL-4-deficient mice, while the numbers of IL-13-expressing CD4 T cells were not affected by IL-4 deficiency indicating that other factors can play a role in directing the development of this Th2 subtype. Taken together, these data indicate that the appearance of IL-4-expressing Tfh cells in the lymph node is not dependent on IL-4 while the appearance of IL-4-expressing Th2 subsets in the lymph node and IL-4, IL-4/IL-13-expressing Th2 subsets in skin and lung tissues of antigen primed mice is significantly IL-4 dependent.

The induction of Th2 responses is thought to be multifactorial, and emerge from specific pathways distinct from those associated with antagonistic antibacterial or antiviral Th1 responses. Here, we show that the recognition of non-viable Nippostrongylus brasiliensis (Nb) in the skin induces a strong recruitment of monocytes and neutrophils and the release of neutrophil extracellular traps (NETs). Nb also activates toll-like receptor 4 (TLR4) signaling with expression of Ifnb transcripts in the skin and the development of an IFN type I signature on helminth antigen-bearing dendritic cells in draining lymph nodes. Co-injection of Nb together with about 10,000 Gram-negative bacteria amplified this TLR4-dependent but NET-independent IFN type I response and enhanced the development of Th2 responses. Thus, a limited activation of antibacterial signaling pathways is able to boost antihelminthic responses, suggesting a role for bacterial sensing in the optimal induction of Th2 immunity.

Building damage from tephra falls can have a substantial impact on exposed communities around erupting volcanoes. There are limited empirical studies of tephra fall impacts on buildings, with none on tephra falls impacting traditional thatched timber buildings, despite their prevalence across South Pacific island nations and parts of Asia. The 2017/2018 explosive eruption of Manaro Voui, Ambae Island, Vanuatu, resulted in damage to traditional (thatched timber), non-traditional (masonry), and hybrid buildings from tephra falls in March/April and July 2018. Field and photographic surveys were conducted across three separate field studies with building characteristics and damage recorded for a total of 589 buildings. Buildings were classified using a damage state framework customised for this study. Overall, increasing tephra thicknesses were related to increasing severity of building damage, corroborating previous damage surveys and vulnerability estimates. Traditional buildings were found to be less resistant to tephra loading than non-traditional buildings, although there was variation in resistance within each building type. For example, some traditional buildings collapsed under ∼40 mm thickness while others sustained no damage when exposed to >200 mm. We attribute this to differences in the pre-eruption condition of the building and the implementation of mitigation strategies. Mitigation strategies included covering thatched roofs with tarpaulins, which helped shed tephra and consequently reduced loading, and providing an internal prop to the main roof beam, which aided structural resistance. As is typical of post-event building damage surveys, we had limited time and access to the exposed communities, and we note the limitations this had for our findings. Our results contribute to the limited empirical data available for tephra fall building damage and can be used to calibrate existing fragility functions, improving our evidence base for forecasting future impacts for similar construction types globally.

Volcanic eruptions can cause significant impacts on communities and infrastructure. There is an increasing need for effective risk assessments to inform decision-making and minimise the impact of volcanic hazards. Vulnerability models play a crucial role in these assessments, connecting the intensity of the hazard with the elements that are exposed to it, allowing for the calculation of potential impact or risk. There has been a large increase in the number of vulnerability models being developed for volcanic risk applications, and there is now a need to identify knowledge gaps for the field to take a strategic approach moving forward. This review aims to provide a high-level overview of the current state of volcanic vulnerability modelling and identify areas for future development. We evaluated 594 vulnerability models covering a range of elements and sectors, including buildings, critical infrastructure, transportation networks, agriculture, and human vulnerability. We reviewed the types of hazard intensity metrics and impact/risk metrics used in the models, modelling methodologies, underpinning data requirements, and uncertainty characterisation. A global clearinghouse for volcanic vulnerability models would be advantageous for the volcanic risk community to identify appropriate vulnerability models quickly and efficiently for their needs. As a first step towards such a clearinghouse, we have uploaded this volcano vulnerability model compilation to a repository and encourage additions/suggestions from the community on its future development. The results of this study will contribute to the advancement of the field and provide valuable insights for future research and development in volcanic risk assessment.

This paper reports the implementation and results of a simulation-based analysis of the impact of cloud/edge-enabled cooperative perception on the performance of automated driving in unsignalized roundabouts. This is achieved by comparing the performance of automated driving assisted by cooperative perception to that of a baseline system, where the automated vehicle relies only on its onboard sensing and perception for motion planning and control. The paper first provides the descriptions of the implemented simulation model, which integrates the SUMO road traffic generator and CARLA simulator. This includes descriptions of both the baseline and cooperative perception-assisted automated driving systems. We then define a set of relevant key performance indicators for traffic efficiency, safety, and ride comfort, as well as simulation scenarios to collect relevant data for our analysis. This is followed by the description of simulation scenarios, presentation of the results, and discussions of the insights learned from the results.

This paper outlines climate emergencies facing universities and, by drawing on research on system transition, provides insights about how change to overcome the challenges might be stewarded. Climate change brings three interconnected and urgent emergencies for universities: (1) Manifest emergencies such as risks to operations and business models; (2) Conceptual emergencies that arise because assumptions, ideologies, systems, and structures cannot match the scale of the manifest challenges; and (3) Existential emergencies where current identities and sense of purpose are incapable of supporting the changes needed to overcome the conceptual challenges. To be viable leaders in the world, universities will need to renew their commitments to serving the public good, be dedicated to an unwavering challenge-orientation, create post-disciplinary structures, and be the change one seeks to see in the world. Importantly, universities will need to overcome the emergencies on the inside if they are to help society address the scale of the challenges on the outside, to which both universities and human capacity are seriously cognitively and emotionally ill-prepared. Fortunately, new insights from research on system transition provide helpful advice on how to steward transformational change. This work highlights that successful transformation requires strong adherence to transformational intent and, in the case of universities, working with all three emergencies simultaneously. Successful transformation will also require harnessing opportunities to disrupt the status quo; supporting an interplay of different forms of management and orientations to the future; developing appropriate infrastructure to support transformation; and rapidly accelerating the development of capacities for transformational change. By actively developing capacities for transformation on the inside universities will then be in a much better position to help and lead others beyond the halls of the academy.