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Rationale: gammadeltaT lymphocytes are enriched within the epithelial microenvironment, where they are thought to maintain homeostasis and limit immunopathology. gammadeltaT cells are postulated to exert a regulatory influence during acute allergic airway disease, but the mechanism is unknown. Although regulation of allergic airway disease has been attributed to IL-17-producing T helper (Th) 17 cells, we have found that gammadeltaT cells represent the major source of IL-17 in the allergic lung.Objectives: The aim of this study was to determine the contribution of these IL-17-producing gammadeltaT cells to regulation of allergic airway inflammation.Methods: Flow cytometry revealed that IL-17-producing gammadeltaT cells are more prevalent than IL-17(+)alphabetaT cells (Th17) in a murine model of ovalbumin-induced allergic inflammation.Measurements and Main Results: Transfer of gammadeltaT cells at the peak of acute allergic responses ameliorated airway hyperresponsiveness with a corresponding acceleration in the resolution of eosinophilic and Th2-driven inflammation. Conversely, functional blockade of gammadeltaT cells led to exacerbation of injury. Neither treatment changed pulmonary Th17 cell numbers. Moreover, transfer of Th17 cells had no effect on disease outcome. Importantly, IL-17-deficient gammadeltaT cells were unable to promote resolution of injury. These data identify IL-17-producing gammadeltaT cells as key regulators of the allergic response in vivo.Conclusions: This unfolds a new perspective for the understanding of gammadeltaT cell function with regard to innate regulation of the adaptive immune responses, emphasizing that resolution of responses are important in determining the outcome of acute inflammatory episodes as well as for maintenance of tissue integrity and homeostasis. [ABSTRACT FROM AUTHOR]

Rationale: Airway hyperreactivity and remodeling are characteristic features of asthma. Interactions between the airway epithelium and environmental allergens are believed to be important in driving development of pathology, particularly because altered epithelial gene expression is common in individuals with asthma.Objectives: To investigate the interactions between a modified airway epithelium and a common aeroallergen in vivo.Methods: We used an adenoviral vector to generate mice overexpressing the transforming growth factor-beta signaling molecule, Smad2, in the airway epithelium and exposed them to house dust mite (HDM) extract intranasally.Measurements and Main Results: Smad2 overexpression resulted in enhanced airway hyperreactivity after allergen challenge concomitant with changes in airway remodeling. Subepithelial collagen deposition was increased and smooth muscle hyperplasia was evident resulting in thickening of the airway smooth muscle layer. However, there was no increase in airway inflammation in mice given the Smad2 vector compared with the control vector. Enhanced airway hyperreactivity and remodeling did not correlate with elevated levels of Th2 cytokines, such as IL-13 or IL-4. However, mice overexpressing Smad2 in the airway epithelium showed significantly enhanced levels of IL-25 and activin A after HDM exposure. Blocking activin A with a neutralizing antibody prevented the increase in lung IL-25 and inhibited subsequent collagen deposition and also the enhanced airway hyperreactivity observed in the Smad2 overexpressing HDM-exposed mice.Conclusions: Epithelial overexpression of Smad2 can specifically alter airway hyperreactivity and remodeling in response to an aeroallergen. Moreover, we have identified novel roles for IL-25 and activin A in driving airway hyperreactivity and remodeling. [ABSTRACT FROM AUTHOR]

Rationale: Although there have been numerous studies on the development of allergen-induced inflammation, the mechanisms leading to resolution of inflammation remain poorly understood. This represents an important consideration because failure to resolve allergen driven inflammation potentially leads to irreversible airway remodeling, characteristic of chronic asthma.Objectives: We investigated the resolution of allergic inflammation and identified the factors responsible.Methods: BALB/c and C57BL/6 mice were sensitized to ovalbumin and challenged through the airways to induce allergic inflammation. Mice were analyzed at 24 hours and 7 days after the final challenge.Measurements and Main Results: Airway hyperreactivity (AHR) and increased mucus production were present 7 days after the cessation of allergen challenge in BALB/c mice. Persisting AHR correlated with the continued presence of Th2 cells but not eosinophils in the lungs. The role of Th2 cells in maintaining AHR was confirmed using blocking antibodies against T1/ST2, IL-4, and IL-13 during the resolution period. Moreover, AHR in the "Th1 type" C57BL/6 mouse strain was resolved 1 week after allergen challenge, concomitant with clearance of Th2 cells from the lung. Expression of the T1/ST2 ligand, IL-33, also correlated with maintenance of AHR.Conclusions: We have used blockade of Th2 function and strain differences to show for the first time that resolution of allergic inflammation and AHR may be dependent on the T1/ST2-IL-33 pathway and the presence of Th2 cells, suggesting they are necessary not only for the development of an allergic response but also for its maintenance. [ABSTRACT FROM AUTHOR]

This Field Note presents a follow-up to a pilot study that explored pre-field placement anxiety for 1st-year MSW students. Previous studies report that students experience significant anxiety as they anticipate their field placement, and research indicates that anxiety has the potential to affect learning. A sample of 204 students reported moderate levels of anxiety, comparable to previous findings. Older students, and those with prior work and classroom experience, reported significantly less anxiety. Students described specific concerns but also viewed anxiety as an expectable response with positive connotations for enhanced learning. Implications for social work education and future research are discussed. [ABSTRACT FROM AUTHOR]

Research has indicated that there is a heightened risk for the occurrence of childhood disabilities in single-parent-female-headed households that are living at or below the poverty line. Research also demonstrates increased levels of parenting stress and parenting depression among mothers who have children with special needs. However, very little is currently known about mental health outcomes among women who are poor and raising children with disabilities To work effectively with these caregivers, human service professionals must utilize multifaceted approaches based on an ecological framework to address the multitude of challenges that these families face. This article draws upon ecological theory and a case study to examine the ways that having a child with special needs impacts women s emotional well-being and their ability to function in roles they deem appropriate for their children. The case study highlights current policies and the ways in which they may exacerbate caretakers' mental health issues. It also provides a framework to identify and demonstrate the ways in which an ecological approach is useful in looking outside the individual and the family to understand the processes through which other systems may interact with the family to affect maternal mental health. Finally, specific links are drawn to both policies and practice. [ABSTRACT FROM AUTHOR]

Background: Airway remodelling is thought to be under the control of a complex group of molecules belonging to the transforming growth factor (TGF)-superfamily. The bone morphogenetic proteins (BMPs) belong to this family and have been shown to regulate fibrosis in kidney and liver diseases. However, the role of BMPs in lung remodelling remains unclear. BMPs may regulate tissue remodelling in asthma by controlling TGF-beta-induced profibrotic functions in lung fibroblasts.Methods: Cell cultures were exposed to TGF-beta1 alone or in the presence of BMP-4 or BMP-7; control cultures were exposed to medium only. Cell proliferation was assessed by quantification of the incorporation of [3H]-thymidine. The expression of the mRNA encoding collagen type I and IV, tenascin C and fibronectin in normal human lung fibroblasts (NHLF) was determined by real-time quantitative PCR and the main results were confirmed by ELISA. Cell differentiation was determined by the analysis of the expression of alpha-smooth muscle actin (alpha-SMA) by western blot and immunohistochemistry. The effect on matrix metalloproteinase (MMP) activity was assessed by zymography.Results: We have demonstrated TGF-beta1 induced upregulation of mRNAs encoding the extracellular matrix proteins, tenascin C, fibronectin and collagen type I and IV when compared to unstimulated NHLF, and confirmed these results at the protein level. BMP-4, but not BMP-7, reduced TGF-beta1-induced extracellular matrix protein production. TGF-beta1 induced an increase in the activity of the pro-form of MMP-2 which was inhibited by BMP-7 but not BMP-4. Both BMP-4 and BMP-7 downregulated TGF-beta1-induced MMP-13 release compared to untreated and TGF-beta1-treated cells. TGF-beta1 also induced a myofibroblast-like transformation which was partially inhibited by BMP-7 but not BMP-4.Conclusions: Our study suggests that some regulatory properties of BMP-7 may be tissue or cell type specific and unveil a potential regulatory role for BMP-4 in the regulation of lung fibroblast function. [ABSTRACT FROM AUTHOR]

The lungs represent a dynamic microenvironment where airway macrophages (AMs) are the major lung-resident macrophages. AMs dictate the balance between tissue homeostasis and immune activation and thus have contradictory functions by maintaining tolerance and tissue homeostasis, as well as initiating strong inflammatory responses. Emerging evidence has highlighted the connection between macrophage function and cellular metabolism. However, the functional importance of these processes in tissue-resident specialized macrophage populations such as those found in the airways, remain poorly elucidated. Here, we reveal that glycolysis is a fundamental pathway in AMs which regulates both lung homeostasis and responses to inhaled allergen. Using macrophage specific targeting in vivo, and multi-omics approaches, we determined that glycolytic activity in AMs is necessary to restrain type 2 (T2) immunity during homeostasis. Exposure to a range of common aeroallergens, including house dust mite (HDM), drove AM-glycolysis and furthermore, AM-specific inhibition of glycolysis altered inflammation in the airways and HDM-driven airway metabolic adaptations in vivo. Additionally, allergen sensitised asthmatics had profound metabolic changes in the airways, compared to non-sensitised asthmatic controls. Finally, we found that allergen driven AM-glycolysis in mice was TLR2 dependent. Thus, our findings demonstrate a direct relationship between glycolysis in AMs, AM-mediated homeostatic processes, and T2 immune responses in the lungs. These data suggest that glycolysis is essential for the plasticity of AMs. Depending on the immunological context, AM-glycolysis is required to exert homeostatic activity but once activated by allergen, AM-glycolysis influences inflammatory responses. Thus, precise modulation of glycolytic activity in AMs is essential for preserving lung homeostasis and regulating airway inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this issue of JEM, Schuijs et al. (https://doi.org/10.1084/jem.20240103) highlight a novel role for basophils during allergic immune responses to house dust mites (HDM). They reveal that interleukin-33 (IL-33)-activated basophils facilitate the recruitment and extravasation of Th2 cells into the lungs during a specific time frame via their interactions with pulmonary endothelial cells., (© 2024 Joulia and Lloyd.)

Background: Wheezing in childhood is prevalent, with over one-half of all children experiencing at least 1 episode by age 6. The pathophysiology of wheeze, especially why some children develop asthma while others do not, remains unclear., Objectives: This study addresses the knowledge gap by investigating the transition from preschool wheeze to asthma using multiomic profiling., Methods: Unsupervised, group-agnostic integrative multiomic factor analysis was performed using host/bacterial (meta)transcriptomic and bacterial shotgun metagenomic datasets from bronchial brush samples paired with metabolomic/lipidomic data from bronchoalveolar lavage samples acquired from children 1-17 years old., Results: Two multiomic factors were identified: one characterizing preschool-aged recurrent wheeze and another capturing an inferred trajectory from health to wheeze and school-aged asthma. Recurrent wheeze was driven by type 1-immune signatures, coupled with upregulation of immune-related and neutrophil-associated lipids and metabolites. Comparatively, progression toward asthma from ages 1 to 18 was dominated by changes related to airway epithelial cell gene expression, type 2-immune responses, and constituents of the airway microbiome, such as increased Haemophilus influenzae., Conclusions: These factors highlighted distinctions between an inflammation-related phenotype in preschool wheeze, and the predominance of airway epithelial-related changes linked with the inferred trajectory toward asthma. These findings provide insights into the differential mechanisms driving the progression from wheeze to asthma and may inform targeted therapeutic strategies., Competing Interests: Disclosure statement The study is supported by a Wellcome Trust grant (108818), a L.E.W. Carty Charitable Fund awarded to C.P., funding from The Hospital Research Foundation Group (2022-SF-EOI-001) awarded to B.J.M. and C.P., and a National Health and Medical Research Council Senior Research Fellowship (1154344) awarded to B.J.M. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Leukotriene A 4 hydrolase (LTA 4 H) is a bifunctional enzyme, with dual activities critical in defining the scale of tissue inflammation and pathology. LTA 4 H classically operates intracellularly, primarily within myeloid cells, to generate pro-inflammatory leukotriene B 4 . However, LTA 4 H also operates extracellularly to degrade the bioactive collagen fragment proline-glycine-proline to limit neutrophilic inflammation and pathological tissue remodeling. While the dichotomous functions of LTA 4 H are dictated by location, the cellular source of extracellular enzyme remains unknown. We demonstrate that airway extracellular LTA 4 H concentrations are governed by the level of pulmonary vascular permeability and influx of an abundant repository of blood-borne enzyme. In turn, blood LTA 4 H originates from liver hepatocytes, being released constitutively but further upregulated during an acute phase response. These findings have implications for our understanding of how inflammation and repair are regulated and how perturbations to the LTA 4 H axis may manifest in pathologies of chronic diseases., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Androgen signaling skews skin immunity toward reduced inflammation in male mice.

Allergic asthma generally starts during early life and is linked to substantial tissue remodeling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLSs), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas. Central to the blood vessel structure, the loss of pericyte coverage was driven by mast cell (MC) proteases, such as tryptase, that can induce pericyte retraction and loss of the critical adhesion molecule N-cadherin. Furthermore, spatial transcriptomics of pediatric asthmatic endobronchial biopsies suggests intense vascular stress and remodeling linked with increased expression of MC activation pathways in regions enriched in blood vessels. These data provide previously unappreciated insights into the pathophysiology of allergic asthma with potential long-term vascular defects.

Background: Preschool wheeze attacks triggered by recurrent viral infections, including respiratory syncytial virus (RSV), are associated with an increased risk of childhood asthma. However, mechanisms that lead to asthma following early-life viral wheezing remain uncertain., Methods: To investigate a causal relationship between early-life RSV infections and onset of type 2 immunity, we developed a neonatal murine model of recurrent RSV infection, in vivo and in silico, and evaluated the dynamical changes of altered airway barrier function and downstream immune responses, including eosinophilia, mucus secretion and type 2 immunity., Results: RSV infection of neonatal BALB/c mice at 5 and 15 days of age induced robust airway eosinophilia, increased pulmonary CD4 + IL-13 + and CD4 + IL-5 + cells, elevated levels of IL-13 and IL-5 and increased airway mucus at 20 days of age. Increased bronchoalveolar lavage albumin levels, suggesting epithelial barrier damage, were present and persisted following the second RSV infection. Computational in silico simulations demonstrated that recurrent RSV infection resulted in severe damage of the airway barrier (epithelium), triggering the onset of type 2 immunity. The in silico results also demonstrated that recurrent infection is not always necessary for the development of type 2 immunity, which could also be triggered with single infection of high viral load or when the epithelial barrier repair is compromised., Conclusions: The neonatal murine model demonstrated that recurrent RSV infection in early life alters airway barrier function and promotes type 2 immunity. A causal relationship between airway barrier function and type 2 immunity was suggested using in silico model simulations., (© 2023 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Allergy is an ever-evolving group of disorders, which includes asthma, atopic dermatitis, rhinitis and food allergies and that currently affects over 1 billion people worldwide. This group of disorders has exploded in incidence since around the start of the 20th century, implying that genetics is not solely responsible for its development but that environmental factors have an important role. Here, Fabio Luciani and Jonathan Coquet, in their role as editors at Immunology & Cell Biology, asked nine prominent researchers in the field of allergy to define the term 'allergy', discuss the role of genetics and the environment, nominate the most important discoveries of the past decade and describe the best strategies to combat allergy at the population level going forward., (© 2023 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

Aberrant expansion of KRT5 + basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5 + cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5 + cells migrate within the fibrotic lung, navigating regional differences in collagen topography. In vitro, KRT5 + cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry- based proteomics revealed compositional differences in ECM components secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrix restricts KRT5 + cell migration in vitro. Together, our findings demonstrate how changes to the ECM in IPF directly influence KRT5 + cell behaviour and function contributing to remodelling events in the fibrotic niche., (© 2023. Springer Nature Limited.)

Asthma is classically considered to be a disease of type 2 immune dysfunction, since many patients exhibit the consequences of excess secretion of cytokines such as IL-4, IL-5, and IL-13 concomitant with inflammation typified by eosinophils. Mouse and human disease models have determined that many of the canonical pathophysiologic features of asthma may be caused by these disordered type 2 immune pathways. As such considerable efforts have been made to develop specific drugs targeting key cytokines. There are currently available multiple biologic agents that successfully reduce the functions of IL-4, IL-5, and IL-13 in patients, and many improve the course of severe asthma. However, none are curative and do not always minimize the key features of disease, such as airway hyperresponsiveness. Here, we review the current therapeutic landscape targeting type 2 immune cytokines and discuss evidence of efficacy and limitations of their use in adults and children with asthma., (© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Respiratory infections are common in infants and young children. However, the immune system develops and matures as the child grows, thus the effects of infection during this time of dynamic change may have long-term consequences. The infant immune system develops in conjunction with the seeding of the microbiome at the respiratory mucosal surface, at a time that the lungs themselves are maturing. We are now recognizing that any disturbance of this developmental trajectory can have implications for lifelong lung health. Here, we outline our current understanding of the molecular mechanisms underlying relationships between immune and structural cells in the lung with the local microorganisms. We highlight the importance of gaining greater clarity as to what constitutes a healthy respiratory ecosystem and how environmental exposures influencing this network will aid efforts to mitigate harmful effects and restore lung immune health., (© 2023. Springer Nature America, Inc.)

Allergic asthma is among the most common immune-mediated diseases across the world, and type 2 immune responses are thought to be central to pathogenesis. The importance of T helper 2 (Th2) cells as central regulators of type 2 responses in asthma has, however, become less clear with the discovery of other potent innate sources of type 2 cytokines and innate mediators of inflammation such as the alarmins. This review provides an update of our current understanding of Th2 cells in human asthma, highlighting their many guises and functions in asthma, both pathogenic and regulatory, and how these are influenced by the tissue location and disease stage and severity. It also explores how biologics targeting type 2 immune pathways are impacting asthma, and how these have the potential to reveal hitherto underappreciated roles for Th2 cell in lung inflammation., (© 2023 Harker and Lloyd.)

Background: Many genes associated with asthma explain only a fraction of its heritability. Most genome-wide association studies (GWASs) used a broad definition of 'doctor-diagnosed asthma', thereby diluting genetic signals by not considering asthma heterogeneity. The objective of our study was to identify genetic associates of childhood wheezing phenotypes., Methods: We conducted a novel multivariate GWAS meta-analysis of wheezing phenotypes jointly derived using unbiased analysis of data collected from birth to 18 years in 9568 individuals from five UK birth cohorts., Results: Forty-four independent SNPs were associated with early-onset persistent, 25 with pre-school remitting, 33 with mid-childhood remitting, and 32 with late-onset wheeze. We identified a novel locus on chr9q21.13 (close to annexin 1 [ ANXA1 ], p<6.7 × 10 -9 ), associated exclusively with early-onset persistent wheeze. We identified rs75260654 as the most likely causative single nucleotide polymorphism (SNP) using Promoter Capture Hi-C loops, and then showed that the risk allele (T) confers a reduction in ANXA1 expression. Finally, in a murine model of house dust mite (HDM)-induced allergic airway disease, we demonstrated that anxa1 protein expression increased and anxa1 mRNA was significantly induced in lung tissue following HDM exposure. Using anxa1 -/- deficient mice, we showed that loss of anxa1 results in heightened airway hyperreactivity and Th2 inflammation upon allergen challenge., Conclusions: Targeting this pathway in persistent disease may represent an exciting therapeutic prospect., Funding: UK Medical Research Council Programme Grant MR/S025340/1 and the Wellcome Trust Strategic Award (108818/15/Z) provided most of the funding for this study., Competing Interests: RG, JC, SH, NK, SM, LG, LY, MT, JH, MP, JV, HA, PC, SF, ST No competing interests declared, GR MRC grant to my institution; President of the British Society of Allergy and Clinical Immunology, GK Dutch Lung Foundation, Ubbo Emmius Foundation (Money to insititution); Dutch Lung Foundation, Vertex, TEVA the Netherlands, GSK, ZON-MW (VICI grant), European Union (Money to institution); Astra Zeneca, Pure IMS, GSK (Money to institution); Sanofi, Boehringer Ingelheim (Money to institution), AS Medical research council Research grant; JP Moulton Charitable Foundation Research grant; Asthma UK Research grant, CM has received grants from Asthma Uk, the National Institute for Health Research, the Moulton Charitable Foundation and the North West Lung Centre Charity (to the Institution). They received lecture fees from GSK and Novartis, and received a travel grant from Sanofi. The authors has no other competing interests to declare, CL Wellcome Trust 107059/Z/15/Z, JH Medial Research Council grant MR/S025340/1 (to institution); American Academy of Allergy Asthma and Immunology (AAAI) (Support for speaker travel to AAAAI annual congress), AC MRC (research grants); EPSRC (research grant); Wellcome Trust (research grant); Worg Pharmaceoticals (Personal payment), (© 2023, Granell et al.)

Introduction: Despite routine implementation of cleaning and disinfection practices in clinical healthcare settings, high-touch environmental surfaces and contaminated equipment often serve as reservoirs for the transmission of pathogens associated with healthcare-associated infections (HAIs)., Methods: The current study involved the analysis of high-touch surface swabs using a metatranscriptomic sequencing workflow (CSI-Dx™) to assess the efficacy of cleanSURFACES® technology in decreasing microbial burden by limiting re-contamination. This is a non-human single center study conducted in the Emergency Department (ED) and on an inpatient Oncology Ward of Walter Reed National Military Medical Center that have followed hygienic practices during the COVID-19 pandemic environment., Results: Although there was no difference in observed microbial richness (two-tailed Wilcoxon test with Holm correction, P > 0.05), beta diversity findings identified shifts in microbial community structure between surfaces from baseline and post-intervention timepoints (Day 1, Day 7, Day 14, and Day 28). Biomarker and regression analyses identified significant reductions in annotated transcripts for various clinically relevant microorganisms' post-intervention, coagulase-negative staphylococci and Malassezia restricta , at ED and Oncology ward, respectively. Additionally, post-intervention samples predominantly consisted of Proteobacteria and to a lesser extent skin commensals and endogenous environmental microorganisms in both departments., Discussion: Findings support the value of cleanSURFACES®, when coupled with routine disinfection practices, to effectively impact on the composition of active microbial communities found on high-touch surfaces in two different patient care areas of the hospital (one outpatient and one inpatient) with unique demands and patient-centered practices., Competing Interests: RL and JRW are owners of Contamination Source Identification, LLC. TTL, CJB, JRCS, SLCA, JP, LP, CYW, and AJS were employed by Contamination Source Identification, LLC. AJS serves as a consultant for AIONX®. JB was employed by AIONX®. ACW was employed by Nextflex. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wright, Ly, Cromwell, Brislawn, Chen See, Anderson, Pellegrino, Peachey, Walls, Lloyd, Jones, Lawrence, Bess, Wall, Shope and Lamendella.)

Communication between nerves and group 2 innate lymphoid cells (ILC2s) is thought to regulate allergic airway inflammation, but the molecular mechanisms are unclear. In this issue of Immunity, Cao et al. uncover an essential role for dopamine in inhibiting ILC2 function via metabolic restriction, thereby ameliorating key features of asthma pathogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: In this study we aimed to determine the impact of the mandatory coronavirus disease 2019 (COVID-19) pandemic stay-at-home order on the proportional makeup of emergency department (ED) visits by frequent users and super users., Methods: We conducted a secondary analysis of existing data using a multisite review of the medical records of 280,053 patients to measure the impact of the COVID-19 pandemic stay-at-home order on ED visits. The primary outcomes included analysis before and during the lockdown in determining ED use and unique characteristics of non-frequent, frequent, and super users of emergency services., Results: During the mandatory COVID-19 stay-at-home order (lockdown), the percentage of frequent users increased from 7.8% (pre-lockdown) to 21.8%. Super users increased from 0.7% to 4.7%, while non-frequent users dropped from 91.5% to 73.4%. Frequent users comprised 23.7% of all visits (4% increase), while super user encounters (4.7%) increased by 53%. Patients who used Medicaid and Medicare increased by 39.3% and 4.6%, respectively, while those who were uninsured increased ED use by 190.3% during the lockdown., Conclusion: When barriers to accessing healthcare are implemented as part of a broader measure to reduce the spread of an infectious agent, individuals reliant on these services are more likely to seek out the ED for their medical needs. Policymakers considering future pandemic planning should consider this finding to ensure that vital healthcare resources are allocated appropriately.

Upon bacterial infection, mounting the appropriate immune response is paramount to effective pathogen clearance. In a recent study, Agaronyan et al. show how Pseudomonas aeruginosa can divert host immunity to boost type 2 responses and drive mucus production, which can then act as a nutrient source for bacteria., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The mammalian airways and lungs are exposed to a myriad of inhaled particulate matter, allergens, and pathogens. The immune system plays an essential role in protecting the host from respiratory pathogens, but a dysregulated immune response during respiratory infection can impair pathogen clearance and lead to immunopathology. Furthermore, inappropriate immunity to inhaled antigens can lead to pulmonary diseases. A complex network of epithelial, neural, stromal, and immune cells has evolved to sense and respond to inhaled antigens, including the decision to promote tolerance versus a rapid, robust, and targeted immune response. Although there has been great progress in understanding the mechanisms governing immunity to respiratory pathogens and aeroantigens, we are only beginning to develop an integrated understanding of the cellular networks governing tissue immunity within the lungs and how it changes after inflammation and over the human life course. An integrated model of airway and lung immunity will be necessary to improve mucosal vaccine design as well as prevent and treat acute and chronic inflammatory pulmonary diseases. Given the importance of immunology in pulmonary research, the American Thoracic Society convened a working group to highlight central areas of investigation to advance the science of lung immunology and improve human health.

Children are less likely than adults to suffer severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while influenza A H1N1 severity is comparable across ages except for the very young or elderly. Airway epithelial cells play a vital role in the early defence against viruses via their barrier and immune functions. We investigated viral replication and immune responses in SARS-CoV-2-infected bronchial epithelial cells from healthy paediatric (n = 6; 2.5-5.6 years old) and adult (n = 4; 47-63 years old) subjects and compared cellular responses following infection with SARS-CoV-2 or Influenza A H1N1. While infection with either virus triggered robust transcriptional interferon responses, including induction of type I (IFNB1) and type III (IFNL1) interferons, markedly lower levels of interferons and inflammatory proteins (IL-6, IL-8) were released following SARS-CoV-2 compared to H1N1 infection. Only H1N1 infection caused disruption of the epithelial layer. Interestingly, H1N1 infection resulted in sustained upregulation of SARS-CoV-2 entry factors FURIN and NRP1. We did not find any differences in the epithelial response to SARS-CoV-2 infection between paediatric and adult cells. Overall, SARS-CoV-2 had diminished potential to replicate, affect morphology and evoke immune responses in bronchial epithelial cells compared to H1N1., (© 2022. The Author(s).)