Journal of Innate Immunity最新文献

{"title":"Pyroptosis regulated by m6A modification: implications for pyroptosis-related disease therapy.","authors":"Yujun Zhou, Bo Wei, Sihan Chen, Xinyang Ren, Rongxin Li, Yi Shen, Xiang Wang, Yuzhen Xia, Siyu Cao, Nan Ding","doi":"10.1159/000552343","DOIUrl":"https://doi.org/10.1159/000552343","url":null,"abstract":"<p><p>Pyroptosis is a lytic and inflammatory form of programmed cell death that is typically initiated by inflammasome activation and executed by gasdermin proteins. It is characterized by cellular swelling, plasma membrane perforation, and the release of intracellular contents. Pyroptosis functions as a \"double-edged sword\" and plays an essential role in defending the host against pathogen invasion when properly regulated; however, excessive or dysregulated pyroptotic activity can contribute to severe inflammatory pathologies. Aberrant pyroptosis is associated with a range of diseases, including sepsis, inflammatory disorders, cancer, atherosclerosis and neurodegenerative disorders. N6-methyladenosine (m6A) modification is among the most abundant and widespread epigenetic modifications in eukaryotic RNAs and influences multiple stages of gene regulation, from messenger RNA processing to protein synthesis. Emerging evidence indicates that m6A modification plays a regulatory role in pyroptosis, suggesting promising avenues for therapeutic intervention in pyroptosis-related diseases. This review provides a systematic delineation of the signalling pathways regulating pyroptosis and a comprehensive analysis of how m6A modification dynamically regulates this form of inflammatory cell death through its writer, eraser, and reader proteins and explores potential molecular triggers of disease progression. We further aimed to elucidate the pathophysiological significance of m6A-mediated regulation of pyroptosis in disease and identify novel therapeutic targets.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-32"},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sCD126 as An Independent Prognostic Biomarker in Critical COVID-19.","authors":"Giorgos Marinakis, Eleni Karakike, Panagiotis Koufargyris, Maria Patrani, Evangelos J Giamarellos-Bourboulis","doi":"10.1159/000552271","DOIUrl":"https://doi.org/10.1159/000552271","url":null,"abstract":"<p><strong>Introduction: </strong>Biomarkers to predict response of critical COVID-19 to tocilizumab (TCZ) are under investigation. Serum levels of interleukin (IL)-6 and IL-6 soluble receptors were studied in a cohort of patients all receiving treatment with TCZ.</p><p><strong>Methods: </strong>In this prospective clinical study, IL-6, soluble (s) CD126 and sgp130 were measured in the serum of 127 patients with critical COVID-19 the first 24 hours from start of mechanical ventilation and before start of TCZ treatment. Outcome was expressed as the World Health Organization Clinical Progression Scale (WHO-CPS) by day 28. The primary endpoint was the identification of a cut-off of the biomarkers which can predict WHO-CPS 6 or more by day 28.</p><p><strong>Results: </strong>Stepwise regression analysis with WHO-CPS ≥6 as the outcome and comorbidities, baseline oxygenation and baseline markers of severity showed that sCD126 ≥100ng/ml is independently associated with worse outcome (Odds ratio 2.42; 95% confidence intervals 1.05 to 5.63; p: 0.039).</p><p><strong>Conclusion: </strong>In a cohort of patients with critical COVID-19 receiving TCZ, sCD126 was a predictor of 28-day outcome.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-8"},"PeriodicalIF":3.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into neutrophil dysfunction in inherited metabolic disorders.","authors":"Anja Wolf, Giulia Montanelli, Déborah Mathis, Andrea Felser, Alexander Lämmle, Jean-Marc Nuoffer, Matthias Gautschi, Carole Bourquin, Darko Stojkov","doi":"10.1159/000552119","DOIUrl":"https://doi.org/10.1159/000552119","url":null,"abstract":"<p><strong>Background: </strong>Inherited metabolic disorders (IMDs) often manifest with defects in neutrophil development, function, or survival, resulting in recurrent severe infections and elevated morbidity. Although neutropenia and immunodeficiency are frequently underrecognized, they are central to the clinical course of several IMDs.</p><p><strong>Summary: </strong>Advances in human genetics and immunometabolism have elucidated the multifaceted mechanisms linking metabolic abnormalities to impaired innate immunity. This review provides a comprehensive analysis of current understanding regarding the pathophysiology, clinical presentation, and management of IMDs with prominent neutrophil involvement, including glycogen storage disease type Ib (GSD-Ib), glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency, glucose-6-phosphate dehydrogenase (G6PD) deficiency, glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1DS1), propionic acidemia (PA), methylmalonic acidemias (MMA), and Barth syndrome (BTHS). We discuss how impaired glucose metabolism, redox imbalance, and disrupted mitochondrial metabolism undermine neutrophil homeostasis and effector function, resulting in increased susceptibility to infections, failure to thrive, and, in some cases, life-threatening inflammatory complications. Emerging therapies, ranging from dietary metabolic or pharmacological interventions to experimental gene therapies, are reshaping clinical management of IMDs.</p><p><strong>Key message: </strong>Rare IMDs involving neutrophil dysfunction reveal essential links between metabolism, intracellular trafficking, and innate immunity. Molecular diagnosis is crucial for guiding targeted treatments, preventing infectious complications, and improve outcomes. Defining the precise immunometabolic disturbance in these diseases not only advances clinical care but also deepens our understanding of neutrophil biology in broader infectious and inflammatory contexts.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-41"},"PeriodicalIF":3.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Streptococcus pyogenes infection and CD4+ T cells crosstalk promote an antigen-presenting cell-like phenotype in neutrophils.","authors":"Anna Riegner, Nikolai Siemens","doi":"10.1159/000551693","DOIUrl":"https://doi.org/10.1159/000551693","url":null,"abstract":"<p><strong>Introduction: </strong>Neutrophils are the most abundant leukocytes in human blood and a key component of host defense against Streptococcus pyogenes (group A streptococci, GAS). They are rapidly recruited to the site of infection, where they mediate phagocytosis, degranulation, and release of neutrophil extracellular traps, thereby influencing both bacterial clearance and tissue damage. Traditionally considered short-lived effector cells, neutrophils are increasingly recognized for their immunomodulatory functions, including regulation of adaptive immunity.</p><p><strong>Methods: </strong>Human neutrophils were infected with GAS wild-type 5448 or isogenic mutants lacking streptolysin O (Δslo) or streptolysin S (ΔsagA) and analyzed either after infection alone or after infection followed by co-culture with autologous CD4⁺ T cells. Neutrophil activation and T cell responses were evaluated via flow cytometry.</p><p><strong>Results: </strong>GAS infection robustly activated neutrophils in a dose-dependent manner, driving expansion of the CD15bright/CD66bbright population and heparin-binding-protein release. Infection prompted neutrophils to acquire APC-like characteristics, including HLA-DR, CD40, and CD86 expression, particularly when exposed to autologous CD4⁺ T cells. In 5448ΔsagA infections, neutrophils showed lower expression of co-stimulatory markers and bacteria were more susceptible to intracellular killing. In co-cultures, CD4⁺ T cells were partially activated, as indicated by CD25 upregulation and Th1- and Th17-cell-associated cytokine release.</p><p><strong>Conclusion: </strong>GAS infected neutrophils acquire an APC-like phenotype and partially modulate CD4⁺ T cell activation, revealing a previously unrecognized role for infected neutrophils in shaping adaptive immunity in streptococcal infections.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-27"},"PeriodicalIF":3.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The challenges of detecting neutrophil CFTR.","authors":"Ryan Flannery, Rory Baird, Debananda Gogoi, Emer P Reeves","doi":"10.1159/000551637","DOIUrl":"https://doi.org/10.1159/000551637","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a hereditary disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The major causes of morbidity and mortality in CF are related to lung disease, involving neutrophil-dominated lung inflammation. Whether the altered inflammatory response of neutrophils in patients with CF is an intrinsic defect due to a lack of CFTR expression, or alternatively, exacerbated by chronic exposure to infection and inflammation, is extensively debated. Fuelling this dispute are conflicting studies on CFTR protein expression by neutrophils, with opposing results described at both the gene and protein level. This is pertinent in the era of CFTR modulator therapies, with clinicians and scientists exploring the impact of different CFTR mutation classes and CFTR modulators on neutrophil function. To address this, the focus of this article is to uncover the cause for the described disparity of data on neutrophil CFTR expression, by investigating methods utilised for CFTR detection, and to draw consensus on the most optimal protocol for identifying CFTR protein in neutrophils.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-16"},"PeriodicalIF":3.0,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory syncytial virus nonstructural protein 1 inhibits production of cytokines and chemokines by differentiated primary nasal epithelial cells cultured at air-liquid interface.","authors":"Rosanne W Koutstaal, Amadeo Munoz Garcia, Nadine Ebert, Manon F Licheri, Anke J Lakerveld, Hendrik-Jan Hamstra, Anne T Gelderloos, Jørgen de Jonge, Cécile A C M van Els, Volker Thiel, Ronald Dijkman, Puck B van Kasteren","doi":"10.1159/000550987","DOIUrl":"https://doi.org/10.1159/000550987","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and older adults. Currently approved vaccines target only the viral fusion protein, but live-attenuated vaccines - e.g. through inactivation of nonstructural protein 1 (NS1) - likely induce a broader immune response. NS1 inhibits the immune response by repressing interferon production, but this has mostly been shown in immortalized cell lines, which do not necessarily represent the in vivo situation. Here, we assessed the effect of NS1 mutations on replication and host responses in physiologically relevant differentiated primary human nasal epithelial cells (HNEC) cultured at air-liquid interface (ALI). Using yeast-based reverse genetics, NS1-inactivating mutations were introduced. In differentiated HNECs, NS1 mutants showed delayed replication compared to wild-type virus. Bulk RNA sequencing early after infection revealed stronger antiviral signatures in HNEC infected with NS1 mutants compared to wild-type, characterized by upregulation of interferons and chemokines. Cytokine analysis confirmed these results. Finally, an indirect immune cell migration assay revealed that both WT and NS1-mutant viruses induce migration of mainly neutrophils. In conclusion, this study shows that RSV NS1 supports viral replication not only via inhibition of the production of interferons, but also by reducing early chemokine production and secretion by epithelial cells. Together, our data highlight the suitability of the ALI transwell model for preclinical assessment of live-attenuated vaccine candidates.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-23"},"PeriodicalIF":3.0,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chloroquine Enhances Mitochondrial Antiviral Signaling-Mediated Cytokine Induction and Alters Mitochondrial Morphology.","authors":"Yu-Ting Kao, Wei-Sheng Chen, Chi-Ting Shie, Chia-Yi Yu","doi":"10.1159/000549390","DOIUrl":"10.1159/000549390","url":null,"abstract":"<p><strong>Introduction: </strong>Chloroquine (CQ), a well-known antimalarial agent, has been proposed as a potential antiviral compound due to its ability to interfere with multiple cellular pathways critical for viral replication. Although CQ exhibits broad-spectrum antiviral activity, its effect on host innate immune responses remains incompletely understood. The timing of CQ administration, whether before or after infection, may lead to different immunological outcomes. Therefore, the immunomodulatory effects of CQ should be carefully evaluated before antiviral therapy.</p><p><strong>Methods: </strong>To investigate the immunomodulatory role of CQ (50 μ<sc>m</sc>), we used immunofluorescence staining, Western blotting, and reporter assays to evaluate innate immune activation in A549 cells. We established a doxycycline-inducible system to activate mitochondrial antiviral signaling (MAVS)-mediated signaling without viral infection. Plaque assays and antiviral tests were performed to measure viral replication, while cytokine array and RT-qPCR were used to quantify cytokine production. Mitochondrial morphology was assessed using immunofluorescence microscopy.</p><p><strong>Results: </strong>CQ enhanced innate immune responses triggered by dengue virus infection and poly(I:C) stimulation. This enhancement was associated with the activation of the MAVS protein and its upstream receptors, including retinoic acid-inducible gene I and melanoma differentiation-associated protein 5. CQ strengthened MAVS-dependent antiviral signaling and increased IL-6 induction more than 13-fold. Alterations in mitochondrial morphology may contribute to this immunostimulatory effect.</p><p><strong>Conclusion: </strong>CQ promotes MAVS-mediated antiviral and inflammatory cytokine responses, potentially through its effect on mitochondrial dynamics. These findings indicate that while CQ may enhance antiviral defense, its immune-stimulating properties should be carefully evaluated prior to its use as an antiviral agent in treating RNA virus infections.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-15"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12726877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil Inflammasome Activation and Pyroptosis Induced by a Metalloproteinase via HIF-1α and Gasdermin D Pathways.","authors":"Milena Daniela Souza Silva, Carolina Pereira da Silva, Vanessa Ferreira de Araujo, Erika Christina Santos de Araujo, Lívia Maria Vieira Brilhante, Hallison Mota Santana, Micaela de Melo Cordeiro Eulálio, Andreimar Martins Soares, Joao Santana da Silva, Sulamita da Silva Setúbal, Alex Augusto Ferreira E Ferreira, Mauro Valentino Paloschi, Juliana Pavan Zuliani","doi":"10.1159/000551301","DOIUrl":"10.1159/000551301","url":null,"abstract":"<p><strong>Introduction: </strong>Bothrops jararacussu venom contains snake venom metalloproteinases (SVMPs) that contribute to inflammation and tissue damage. BjussuMP-II, a PI class SVMP, lacks hemorrhagic activity but retains proteolytic and immunomodulatory properties.</p><p><strong>Methods: </strong>Here, we uncover a previously unrecognized function of BjussuMP-II in triggering NLRP3 inflammasome activation in human neutrophils, leading to IL-1β release and pyroptosis. Inflammasome activation was investigated through gene expression analysis by quantitative PCR and protein expression by immunoblotting. Caspase-1 activation and gasdermin D (GSDMD) cleavage were assessed to confirm pyroptotic signaling. Pharmacological inhibition assays were performed to dissect the involvement of specific signaling pathways, and IL-1β secretion was quantified by enzyme immunoassay. This discovery reveals a direct molecular link between SVMP activity and inflammasome-mediated inflammation, a fundamental mechanism with implications beyond snakebite pathology. It highlights inflammasomes as potential therapeutic targets to mitigate severe inflammatory responses in envenomed patients.</p><p><strong>Results: </strong>Mechanistically, BjussuMP-II increased expression of NLRP3, ASC, caspase-1, NEK7, and HIF-1α, as well as IL-1β and GSDMD cleavage, confirmed by immunoblotting and immunofluorescence. It promoted the release of IL-1β, LTB₄, LDH, and dsDNA, consistent with pyroptosis, and this release was reduced by MCC950 or disulfiram. Studies in Gsdmd-/- and HIF-1α-deficient neutrophils further demonstrated the requirement of these pathways for cytokine release.</p><p><strong>Conclusion: </strong>Collectively, these results indicate that BjussuMP-II modulates inflammasome-associated signaling pathways in neutrophils, contributing to the inflammatory responses triggered by SVMPs.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"169-187"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-6 Limits Host Susceptibility to Urinary Tract Infection by Promoting Urothelial Expulsion of Intracellular Bacteria.","authors":"Sudipti Gupta, Shradha Rajak, Hanna Cortado, Brian Becknell, John David Spencer, Christina Barbara Ching","doi":"10.1159/000550787","DOIUrl":"10.1159/000550787","url":null,"abstract":"<p><strong>Introduction: </strong>Interleukin (IL)-6 has an important role in limiting urinary tract infection (UTI). Mice lacking IL-6 are more susceptible to uropathogenic Escherichia coli (UPEC), including increased formation of intracellular bacterial communities (IBCs). How IL-6 promotes UPEC clearance is unknown. We hypothesize IL-6 reduces UTI susceptibility by limiting IBC formation through an early mechanism of infection.</p><p><strong>Methods: </strong>Female mice were treated with vehicle or neutralizing antibodies to inhibit IL-6 or the IL-6 receptor (IL-6R) prior to transurethral UPEC infection. In rescue experiments, murine recombinant (r)IL-6 was administered to IL-6 knockout (KO) mice. Bladder IBCs, urinary and bladder bacterial burden, and UPEC expulsion were quantified. For clinical translation, human urothelial cells were pretreated with human rIL-6 and infected with UPEC. Bacterial attachment, invasion, and expulsion were quantified.</p><p><strong>Results: </strong>Neutralization of IL-6 or IL-6R increased bladder IBC counts compared to isotype controls. Similarly, while IL-6 KO mice exhibited higher IBC counts than wild-type controls, this phenotype was reversed by rIL-6 administration. Gentamicin protection assays confirmed increased intracellular UPEC burden and reduced bacterial expulsion in IL-6 KO bladders. rIL-6 treatment enhanced UPEC expulsion in human urothelial cells without impacting bacterial attachment or invasion.</p><p><strong>Conclusion: </strong>IL-6 facilitates UPEC expulsion, limiting intracellular UPEC early in infection and thus the initial formation of IBCs. Since IBC formation is a bottleneck in UPEC survival during UTI, these findings identify a mechanism whereby IL-6 reduces early UPEC urothelial infectivity.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"120-125"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalation of N-Chlorotaurine Is an Effective Treatment of <italic>Aspergillus fumigatus</italic> Pneumonia in Mice.","authors":"Cornelia Speth, Günter Rambach, Andrea Windisch, Nadine Falbesoner, Christoph Schatz, Georg Schäfer, Markus Nagl","doi":"10.1159/000550140","DOIUrl":"10.1159/000550140","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;N-chlorotaurine (NCT), a long-lived oxidant of human granulocytes, can be used topically as anti-infective in different body regions. The aim of the present study was to demonstrate the efficacy and tolerability of inhaled NCT in a mouse model of Aspergillus fumigatus pneumonia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Specific pathogen-free female C57BL/6JRj mice were immune-suppressed with cyclophosphamide or cortisone acetate. After 7 days, they were inoculated intranasally with 6.5 × 106 spores of A. fumigatus. Treatment with aerosolized (&lt;5 µm) aqueous 0.1%, 0.5%, 1.0%, or 2.0% NCT solution or 0.9% sodium chloride as placebo three times daily for 10 min was started 1 h after inoculation and ended after 14-16 days. Prophylactic treatment exclusively for 2 days before infection was investigated additionally. Main parameters of evaluation were survival and fungal load in the lung homogenate, secondary ones clinical (body weight, organ weights, body temperature) and blood inflammation parameters, bronchoalveolar lavage fluid analysis, and histology of organs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Pneumonia occurred in all mice, but the survival was much higher in animals treated with NCT compared to placebo. In placebo groups, 8/9 mice observed for 15 days died from the infection during this time, while 0/9 to 1/9 died in groups treated with 0.5%, 1.0%, and 2.0% NCT (p &lt; 0.01 for each concentration versus saline). There was no difference between the two ways of immune-suppression. With 0.1% NCT, 4/9 mice died (p = 0.029 versus 0.5% and 2.0% NCT; p = 0.0035 versus control). The fungal load came to 5.28 log&lt;sub&gt;10&lt;/sub&gt; (4.46; 5.70; median, quartiles) colony-forming units per ml lung homogenate in the control group and to 1.3 log&lt;sub&gt;10&lt;/sub&gt; (median; maximum 2.45) in the 1% NCT group in mice immune-suppressed with cyclophosphamide (p = 0.0004). Values were similar in cortisone groups (p = 0.0023). Of note, the prophylactic inhalations with 1% NCT were equally effective. Loss of body weight was significantly higher in the control animals compared to the test ones. Organ weights of the lung, brain, and kidney were significantly higher in the control groups than in the test groups, while the opposite was found for the spleen weight with more lymphatic hyperplasia in the test animals. Mice treated with 2.0% NCT had a breath sound for a few minutes after inhalation, but no further hints for incompatibility or discomfort could be detected.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Early treatment with inhaled NCT as well as prophylactic treatment demonstrated a highly significant beneficial efficacy in Aspergillus pneumonia. A concentration around 1% NCT appears to be optimal taking into account both tolerability and efficacy, which is in agreement with previous studies and case experiences in humans. Inhalation with NCT as an antiseptic and anti-infective product of granulocytes is highly promising in infections of the lower airways and sh","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"35-51"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}