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Journal articleFarias A, Bridgeman VL, Rodrigues FS, et al., 2026, , Proc Natl Acad Sci U S A, Vol: 123
Metastatic breast cancer accounts for 7% of cancer-related deaths, with the lungs being a common site of cancer spread. In parallel, lower respiratory tract infections, including those caused by respiratory syncytial virus (RSV), remain a common cause of morbidity and mortality worldwide. Acute viral respiratory infections induce marked changes in the lung. However, how these changes influence metastasis initiation and cancer progression remains unclear. Using breast cancer and other cancer cell types in an experimental lung metastasis model, we show that RSV infection impairs tumor cell seeding and early growth in the lung, resulting in fewer metastatic nodules. We demonstrate that restriction of metastatic spread is due to alterations in the lung environment mediated by RSV-induced type I interferons (IFNs). Consistent with this idea, intranasal administration of recombinant IFN-α is sufficient to recapitulate the anti-metastatic effect of RSV infection. Using single cell RNA sequencing supported by in vivo and ex vivo validation, we show that IFN-α influences interactions between epithelial/endothelial cells and cancer cells. Furthermore, both RSV infection and IFN-α administration trigger marked local and systemic upregulation of Galectin-9, an IFN-inducible protein associated with acute respiratory infection in humans. Treatment of cancer cells with Galectin-9 alone is sufficient to restrict metastatic seeding. Altogether, our results suggest that type I IFNs induced by respiratory virus infection render the lungs less permissive to cancer cell seeding and consequently interfere with the ability of tumor cells to successfully initiate metastatic colonization.
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Journal articleSinadinos A, Bell R, Juarez-Molina CI, et al., 2026, , Molecular Therapy Advances, ISSN: 3117-387X
Targeting of the nasal epithelium for sustained therapeutic protein secretion represents a potential non-invasive lentiviral vector application strategy. Using reporter imaging, molecular, and radiopharmaceutical tracing methods in mice, we have developed an intranasal (nose-only) dosing strategy with a Sendai-virus envelope glycoprotein pseudotyped lentiviral vector (rSIV.F/HN). Using multiple (up to 10) small volume (5 μL) intranasal bolus applications, technetium radiotracer showed >90% liquid retention in the murine head and <1% in the lung. Following vector administration, transgene expression was dose-related in the nose with minimal lung expression. No acute nasal toxicity was associated with nose-only delivery. Next, we compared levels of a secreted protein, Gaussia luciferase (Gluc), in the airways and serum after nose-only and intravenous administration of rSIV.F/HN-Gluc (2e8 TU/mouse). Gluc expression in the nose and lungs was higher following nose-only versus intravenous administration. Serum levels were similar after either route of administration. Finally, nose-only delivery of rSIV.F/HN encoding GM-CSF, led to sufficient lung levels of this therapeutic protein to correct disease biomarkers in a mouse model of pulmonary alveolar proteinosis. We conclude that non-invasive administration of a lentiviral vector to the nasal epithelium provides a safe and convenient route for secreted protein production and is readily translatable into humans.
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Journal articleJackson R, Bentley S, Davies JC, et al., 2026, , Paediatr Respir Rev
The availability of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators has transformed outcomes for people with cystic fibrosis (pwCF). Eligibility, conferred initially by clinical trial data, has evolved through advances in in vitro 'theratyping' and use of real‑world evidence. Since ivacaftor's approval for a single gating variant in 2012, eligibility has broadened to over 180 variants with the highly effective therapies elexacaftor/tezacaftor/ivacaftor and recently launched vanzacaftor/tezacaftor/deutivacaftor. Regulatory authorities have increasingly accepted non‑traditional evidence, notably the FDA's 2017 ivacaftor extension based on cell‑based assays and, in 2025, the EMA's decision to extend elexacaftor/tezacaftor/ivacaftor to people ≥2 years with at least one non class I variant. However, clinical response remains variable, influenced in part by baseline characteristics, pharmacokinetics, pharmacogenetics, and environmental exposures. We outline evolving approaches to determining eligibility and strategies to improve methods to predict, verify, and monitor clinical response in an era of personalised medicine.
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Journal articleBokobza I, Wilson G, Downes A, et al., 2026, , American Journal of Respiratory and Critical Care Medicine
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Journal articleGriesenbach U, McLachlan G, Sinadinos A, et al., 2026, , Molecular Therapy Advances, Vol: 34, Pages: 201655-201655, ISSN: 3117-387X
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Journal articleBarnes M, Stretch S, Swieboda D, et al., 2026, , Mucosal Immunology, ISSN: 1933-0219
RationaleBronchiolitis is the commonest cause of hospital admission in children under the age of 1 year, most cases being due to respiratory syncytial virus (RSV) infection. The mechanisms causing infantile bronchiolitis are incompletely understood but include a deficient mucosal interferon response, neutrophilic inflammation and enhanced mucosal Type-2 responses.ObjectivesWe sought to determine the mucosal immune processes associated with severe paediatric bronchiolitis.MethodsWe performed transcriptomic analyses on mucosal samples from infants hospitalized with Moderate (n = 48) and Severe (n = 40) bronchiolitis. Differential expression and regression analyses determined genes associated with different severity categories. Responses were modelled in vitro using air–liquid interface human nasal epithelial cell culture models.Measurements and main resultsWe confirmed weakened interferon-associated signalling in severe RSV and non-RSV bronchiolitis but unexpectedly found elevated IL-36α (an IL-1 family cytokine implicated in chronic inflammatory diseases) early in infection. Conversely, IL36A was decreased in whole blood during severe RSV, suggesting that this association is unique to the mucosa. In human nasal epithelial cells grown in vitro under air–liquid interface we found IL-36α to be produced by epithelial cells during RSV infection and that its secretion is enhanced by neutrophils.ConclusionsThese findings implicate mucosal IL-36α as a dominant feature of severe paediatric bronchiolitis.
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Journal articleSanchez-Garcia MA, Sadiku P, Ortmann BM, et al., 2026, , Nature Immunology, Vol: 27, ISSN: 1529-2908
Correction to: Nature Immunology https://doi.org/10.1038/s41590-025-02301-9, published online 28 October 2025.In the version of this article initially published, the surname of Musa M. Mhlanga was misspelled (Mhalanga) and is now amended in the HTML and PDF versions of the article.
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Journal articleWagstaffe HR, Thwaites RS, Sidhu JK, et al., 2026, , Nature Communications, Vol: 17, ISSN: 2041-1723
Identifying host factors that mediate protection during first exposure to newly emergent viruses may assist in responding to future pandemics. Here, we report correlates of protection in a controlled human infection model of SARS-CoV-2 in serologically naïve individuals (n=34, aged 18-29 years) inoculated with 10 TCID50 of a D614G-containing pre-Alpha variant SARS-CoV-2. Eighteen developed “sustained infection” and seroconverted, while the remaining 16 did not. Pre-exposure and early immune factors associated with resisting infection were comprehensively analysed using multiplex protein, cytometric and RNA sequencing approaches in the upper respiratory mucosa and circulation. Associations between pre-existing antibody level and outcome suggested a modest role for cross-reactive antibodies in protection, with baseline nasal anti-SARS-CoV-2 Spike IgM levels correlating with delayed infection onset. Instead, resistance to infection was associated with heightened nasopharyngeal CCL13 levels produced locally by conventional dendritic cells and monocytes. Cross-reactive IL-2 producing T cells against SARS-CoV-2 non-structural proteins and less differentiated NK cells were also enriched at the time of inoculation in these individuals. This was followed by increased numbers of innate and adaptive cellsin the nasopharynx, including resident memory T cells, within 24 hours of virus exposure. Conditional independence network analysis revealed nasal CCL13 as the central node in a module associated with protection, connected to pre-existing RTC-specific T cells by CD1c+ DCs. In those who became infected, higher baseline cross-reactive T cell and less differentiated NK cell frequencies also correlated with shorter duration of infection. Thus, enhanced pre-existing mucosal chemokine levels may enable rapid immune cell recruitment and antigen-presentation to resident T cells in respiratory mucosa, effectively blocking infection. Where this local response fails to c
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Journal articleMartyn O, Vlasich C, Khariv V, et al., 2026, , Reviews in Medical Virology, Vol: 36, ISSN: 1052-9276
Parainfluenza virus (PIV) is a common cause of respiratory illness in children and immunocompromised adults, but little is known about its epidemiology or disease burden in the general adult population. This review evaluates published global epidemiological and disease burden for PIV in adults, including high-risk patients (immunocompromised or with chronic illnesses), and identifies existing data gaps. A PRISMA systematic review of publications from 2014 to 2023 in PubMed reporting PIV prevalence and disease burden (including hospitalisations, mortality) in adults (≥ 18 years) and high-risk patients was performed. Sixty-five studies were included; which skewed towards Asia, Europe, and North America, highlighting a data gap in global PIV prevalence. Overall prevalence of PIV (all strains) ranged from 0 to 15.2% [median 2%] in the general adult population (not considered high-risk but tested for infection). PIV3 was the most prevalent strain (0.6−15.2% [2.9]), followed by PIV4 (0.4−6.5% [1.9]), PIV1 (0.5−2.8% [1.1]), and PIV2 (0−2.9% [1.1]). PIV prevalence was generally higher in high-risk adults (up to 41% in certain risk groups) and those aged ≥ 65. Mortality rates ranged from 2 to 40% in those high-risk, while need for respiratory assistance ranged from 0.9% to 64.2% and hospitalisation from 3.7% to 45.3%. None of the studies reported cost-related healthcare resource utilisation. Variability of study designs, data stratification, and patient populations in the selected studies challenged evaluating the true prevalence of PIV and its burden. PIV infection carries an underappreciated burden, with substantial morbidity and mortality risks, especially in high-risk patients. Significant knowledge gaps exist regarding global prevalence and economic burden in the general adult population.
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Journal articleJia X, Foo IJ, McQuilten HA, et al., 2026, , Clin Transl Immunology, Vol: 15, ISSN: 2050-0068
OBJECTIVES: Our previous study in hospitalised patients infected with avian A(H7N9) influenza virus identified CD84 amongst several genes associated with recovery. Yet, the correlation between CD84 and respiratory viral infection outcomes is far from established. We aimed to define CD84 dynamics in patient cohorts of respiratory disease and immune cell populations in influenza virus-infected mice. METHODS: Expression dynamics of CD84 and association with previously identified correlates of severe and fatal respiratory disease outcomes, OLAH and IL18R1, were analysed in A(H7N9) and COVID-19 patient cohorts across disease severities. Using mouse models of influenza virus infection, CD84 expression on immune cell subsets was analysed over the course of infection. RESULTS: Elevated CD84 levels in recovered A(H7N9) patients were accompanied by increased expression of genes for CD84-associated adaptor proteins and other SLAM receptor family members. In these patients, high CD84 expression persisted until discharge, while remaining low throughout the disease in patients that succumbed. We found inverse correlations between CD84 with OLAH and IL18R1 levels in our A(H7N9) cohort, and in hospitalised COVID-19 patients across respiratory disease severities. In influenza virus-infected mice, CD84 was upregulated on a broad range of immune cell populations, particularly on activated and influenza virus-specific T-cell populations and correlated with less disease severity. CONCLUSION: Our findings revealed the link between high CD84 expression in humans and recovery from respiratory viral infections. In mice, CD84 expression increased across a broad range of immune cell populations, with CD84 expression on activated T-cell populations correlating with less severe disease.
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