Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleNguyen THO, Rowntree LC, Chua BY, et al., 2024,
Defining the balance between optimal immunity and immunopathology in influenza virus infection
, Nature Reviews Immunology, Vol: 24, Pages: 720-735, ISSN: 1474-1733Influenza A viruses remain a global threat to human health, with continued pandemic potential. In this Review, we discuss our current understanding of the optimal immune responses that drive recovery from influenza virus infection, highlighting the fine balance between protective immune mechanisms and detrimental immunopathology. We describe the contribution of innate and adaptive immune cells, inflammatory modulators and antibodies to influenza virus-specific immunity, inflammation and immunopathology. We highlight recent human influenza virus challenge studies that advance our understanding of susceptibility to influenza and determinants of symptomatic disease. We also describe studies of influenza virus-specific immunity in high-risk groups following infection and vaccination that inform the design of future vaccines to promote optimal antiviral immunity, particularly in vulnerable populations. Finally, we draw on lessons from the COVID-19 pandemic to refocus our attention to the ever-changing, highly mutable influenza A virus, predicted to cause future global pandemics.
-
Journal articleDiaz-Nicieza C, Sahyoun L, Michalaki C, et al., 2024,
Ageing results in an exacerbated inflammatory response to LPS by resident lung cells
, Immunity and Ageing, Vol: 21, ISSN: 1742-4933BackgroundAgeing is associated with an increased risk of lung infection and chronic inflammatory lung disease. Innate immune responses are the first line of defence in the respiratory tract, however, age related changes to innate immunity in the lung are not fully described. Both resident haematopoietic cells, such as alveolar macrophages, and non-haematopoeitic cells, such as epithelial and endothelial cells can contribute to inflammatory and immune responses in the lung. In this study we aimed to determine the impact of ageing on early innate responses of resident cells in the lung. ResultsAged and young mice were inoculated intranasally with lipopolysaccharide (LPS). After 4h, aged mice recruited higher numbers of neutrophils to the airways and lung. This exacerbated inflammatory response was associated with higher concentrations of chemokines CXCL1, CXCL2 and CCL2 in the airways. Next, precision cut lung slices (PCLS) were stimulated ex vivo with LPS for 16h. Gene expression of Cxcl2, Tnf and Il1b were all higher in PCLS from aged than young mice and higher levels of secretion of CXCL2 and TNF were detected. To determine which lung cells were altered by age, LPS was intranasally administered to aged and young mice and individual populations of cells isolated by FACS. RT-PCR on sorted cell populations demonstrated higher expression of inflammatory cytokines Cxcl2, Ccl2 and Tnf in epithelial cells and alveolar macrophages and higher expression of Cxcl2 by endothelial cells of aged mice compared to young. These differences in expression of pro-inflammatory cytokines did not correspond to higher levels of Tlr4 expression.ConclusionsAgeing leads to a heightened neutrophilic inflammatory response in the lung after LPS exposure, and higher expression and production of pro-inflammatory cytokines by resident lung cells, including alveolar macrophages, epithelial cells and endothelial cells. The responses of multiple resident lung cell populations are altered by aging and
-
Book chapterLiew F, Openshaw PJM, 2024,
Long COVID: current management and future prospects
, COVID-19: An Update, Editors: Chalmers, Cilloniz, Cao, Publisher: European Respiratory Society, Pages: 250-277, ISBN: 9781849841818Long COVID is a chronic and debilitating condition with limited treatment options, suffered by millions of people globally. In the absence of diagnostic biomarkers and defined pathobiological mechanisms, symptom control and rehabilitation are currently the mainstays of management. A variety of clinical trials are underway, but many fail to take into account the pathogenic subgroups of long COVID. Characterising these subgroups and elucidating their associated pathophysiology would enable targeted trials of disease-modifying treatments. Adaptive multidisciplinary trials using defined disease subgroups, biomarkers and end-points are required to optimise clinical interventions.
-
Journal articleShort C, Semple T, Abkir M, et al., 2024,
Assessing pulmonary exacerbations (PEx) in people with cystic fibrosis (pwCF) with dynamic functional lung MRI
, European Respiratory Journal, Vol: 64, ISSN: 0903-1936 -
Journal articleRoutley C, Walker S, Alton EWFW, et al., 2024,
Fixing lung health in the UK: accelerating respiratory research and innovation
, THORAX, Vol: 79, Pages: 809-810, ISSN: 0040-6376 -
Journal articleChesshyre E, Warren FC, Shore AC, et al., 2024,
Long-term outcomes of allergic bronchopulmonary aspergillosis and Aspergillus colonization in children and adolescents with cystic fibrosis
, Journal of Fungi, Vol: 10, ISSN: 2309-608XObservational studies indicate that Aspergillus colonization and allergic bronchopulmonary aspergillosis (ABPA) in people with cystic fibrosis (CF) are associated with poorer lung health and increased disease severity. We performed a longitudinal observational cohort study to analyse long-term outcomes of Aspergillus colonization and ABPA in children with CF. Anonymised UK CF Registry data from 2009 to 2019 for patients aged 8–17 years in 2009–2010 were collected. For the baseline cohort analysis, patients were classified based on the presence of Aspergillus colonization and ABPA in 2009 and/or 2010. For the longitudinal analysis, patients were categorised according to annual Aspergillus colonization and ABPA status. Comparisons made were (1) Aspergillus positive vs. negative; (2) excluding those with ABPA: Aspergillus positive vs. negative; and (3) ABPA positive vs. negative. Primary outcome was percentage predicted FEV1 decline and secondary outcomes included BMI decline, mortality, lung transplant, and IV antibiotic use. Of the 1675 children, 263 had Aspergillus colonization in the baseline cohort, 260 were diagnosed with ABPA, and 80 had both. Baseline cohort analysis showed significantly lower lung function (p < 0.0001) and increased antibiotic treatment (p < 0.001) in those with Aspergillus colonization and in those with ABPA. Longitudinal analysis showed ABPA was associated with increased decline in lung function (p < 0.00001) and BMI (p < 0.00001). Aspergillus colonization was associated with increased decline in BMI (p = 0.005) but not lung function (p = 0.30). ABPA was associated with increased decline in long-term lung function and BMI in children and young people with CF. Aspergillus colonization was associated with lower lung function at baseline, but no increased rate of decline was observed long-term.
-
Journal articleJia X, Crawford JC, Gebregzabher D, et al., 2024,
High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases
, Cell, Vol: 187, Pages: 4586-4604, ISSN: 0092-8674Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah-/- mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease.
-
Journal articleDobra R, Carroll S, Davies JC, et al., 2024,
Exploring the complexity of cystic fibrosis (CF) and psychosocial wellbeing in the 2020s: current and future challenges
, Paediatric Respiratory Reviews, ISSN: 1526-0542Cystic fibrosis (CF) is traditionally associated with considerable and progressive multisystem pathology, onerous treatment burden, complex psychosocial challenges, and reduced life-expectancy [1], [2], [3], [4], [5], [6], [7], [8], [9].This decade has seen transformative change in management for many, but not all, people with CF. The most notable change comes from Cystic Fibrosis Transmembrane Receptor (CFTR) modulators, which bring significant benefits for people who are eligible for, and able to access, them [10]. However alongside, or perhaps because of, this exciting progress, the past few years have also brought important novel challenges to the psychosocial wellbeing of people with CF.This article, written as a collaboration between CF psychologists, social workers, physicians and nurses aims to provide an accessible overview of the novel psychosocial challenges now faced by children, their families, and adults with CF, and to invite consideration of their changing psychosocial requirements to inform future holistic care. Themes include geopolitical stressors such as the pandemic and its wake, a growing divide between those able or unable to access CFTR modulators, potential rapid changes in life expectancy secondary to these drugs and the inevitable associated challenges this brings; evolving body image, mental health side effects of CFTR modulators, the challenges of adherence in apparently well children and young adults, as well as the diagnostic conundrum and associated anxiety of the cystic fibrosis screen positive inconclusive diagnosis (CFSPID) label. It also highlights some unmet research and service delivery needs in the area.
-
Journal articleMall MA, Burgel P-R, Castellani C, et al., 2024,
Cystic fibrosis
, Nature Reviews Disease Primers, Vol: 10, ISSN: 2056-676XCystic fibrosis is a rare genetic disease caused by mutations in CFTR, the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). The discovery of CFTR in 1989 has enabled the unravelling of disease mechanisms and, more recently, the development of CFTR-directed therapeutics that target the underlying molecular defect. The CFTR protein functions as an ion channel that is crucial for correct ion and fluid transport across epithelial cells lining the airways and other organs. Consequently, CFTR dysfunction causes a complex multi-organ disease but, to date, most of the morbidity and mortality in people with cystic fibrosis is due to muco-obstructive lung disease. Cystic fibrosis care has long been limited to treating symptoms using nutritional support, airway clearance techniques and antibiotics to suppress airway infection. The widespread implementation of newborn screening for cystic fibrosis and the introduction of a highly effective triple combination CFTR modulator therapy that has unprecedented clinical benefits in up to 90% of genetically eligible people with cystic fibrosis has fundamentally changed the therapeutic landscape and improved prognosis. However, people with cystic fibrosis who are not eligible based on their CFTR genotype or who live in countries where they do not have access to this breakthrough therapy remain with a high unmet medical need.
-
Journal articleMarchal A, Cirulli ET, Neveux I, et al., 2024,
Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection
, HGG Advances, Vol: 5, ISSN: 2666-2477Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.
