Frontiers in Immunology最新文献

Introduction: Aspergillus fumigatus (A. fumigatus) conidia have been reported to induce inflammatory response in macrophages, resulting in lung damage. However, the role of secondary metabolites secreted by conidia during the infection process remains unclear. Our objective is to investigate the metabolic changes produced by conidia at different developmental stages and to assess the effects of the conidial supernatant on the inflammatory response of macrophages.

Methods: We employed optical microscopy, electron microscopy, and nuclear division staining to identify the morphological characteristics of the Aspergillus fumigatus strain Af293 conidia at various developmental stages. Metabolomic analysis of the supernatant from conidial pre-germination (Af293-4h) and post-germination (Af293-12h) was performed using Liquid Chromatography-Mass Spectrometry. Conidial supernatant was utilized to stimulate mouse alveolar macrophages (MH-S) cells, and the expression of inflammatory factors was quantified using ELISA and RT-qPCR. Western blotting was conducted to detect the levels of key proteins involved in the inflammatory pathway. Furthermore, mice were administered an intranasal instillation of the supernatant to construct the pneumonia model, and lung pathology was evaluated through hematoxylin-eosin (HE) staining, while the levels of inflammatory factors in bronchoalveolar lavage fluid were assessed using ELISA and RT-qPCR.

Results: Non-targeted metabolomics analyses reveal an increased secretion of organic acids and their derivatives, lipids and lipid-like molecules, phenolic compounds, phenylpropanoids, polyketides, as well as alkaloids and their derivatives following conidial germination. Compared to Af293-4h supernatant, Af293-12h supernatant induce a significantly stronger inflammatory response in MH-S cells, characterized by the increased expression of inflammatory factors, including IL-1β, TNF-α, CCL/CXCL and MMPs, via the activation of JAK/STAT/AKT and MAPK signaling pathways. Nasal exposure of conidial supernatant in mice can induce lung inflammation, resulting in lung damage and an elevated proportion of inflammatory cells, as well as increased levels of the inflammatory factors such as TNF-α, IL-1β, and IL-6.

Conclusion: Our research indicates significant differences in the metabolites of A. fumigatus conidial supernatant between the pre-germination and post-germination stages. The conidial supernatant can induce a pronounced inflammatory response in macrophages, mediated by the activation of the JAK/STAT/MAPK pathways. Long-term exposure to spore supernatant in mice can result in pneumonia and tissue damage.

Severe fever with thrombocytopenia syndrome (SFTS), caused by the SFTS virus (SFTSV), has emerged as a significant global public health threat. Infected patients may present with gastrointestinal, neurological, and cardiovascular ribavirin and favipiravir are currently used in clinical practice, their efficacy remains controversial, and treatment primarily relies on symptomatic and supportive care. To date, there is no standard treatment regimen for SFTSV infection, nor are there any approved vaccines. However, recent advances in SFTSV research and the application of novel technologies have opened new pathways for the development of antiviral drugs and vaccines. This review summarizes the latest progress in the development of therapeutic agents and vaccines against SFTSV, aiming to provide valuable insights for drug development and countermeasure strategies for SFTS.

Purpose: COPB1 encodes the coatomer subunit beta protein, which is essential for brain development and intracellular protein trafficking. Homozygous mutations cause Baralle-Macken syndrome that characterized by global developmental delay, severe intellectual disability, and early-onset cataracts. Although immunodeficiency has been observed in patients with COPB1 deficiency, the immunological phenotype remains incompletely characterized. Here, we comprehensively describe the clinical features and delineate the immunological phenotype associated with COPB1 mutations.

Methods: We performed detailed clinical and immunological evaluations of three female siblings with COPB1 deficiency. Flow cytometry was used to characterize lymphocyte subsets and to assess cytokine secretion following stimulation. Functional proliferation of peripheral blood mononuclear cells (PBMCs) was assessed using dye labeling, CD3/CD28 activation, and flow cytometric analysis.

Results: Three female siblings with COPB1 deficiency presented with early-onset cataracts, global developmental delay, hypotonia, and progressive spasticity leading to quadriplegia. All patients experienced recurrent infections beginning in early childhood. Immunological evaluation revealed neutropenia, T cell lymphopenia, profound reduction in switched and unswitched memory B cells, and absent specific antibody responses. All the three patients were initiated on immunoglobulin replacement therapy and antimicrobial prophylaxis.

Conclusion: Our findings expand the clinical and immunological spectrum of COPB1 deficiency, demonstrating combined immunodeficiency with neutropenia, lymphopenia and impaired specific antibody responses. These results support the classification of COPB1 deficiency as a combined immunodeficiency with syndromic features under the IUIS classification system and emphasize the importance of comprehensive immunological evaluation and early immunoglobulin replacement therapy in patients with COPB1 mutations.

Background: Neutralising antibodies and infection with the newest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant NB.1 in Chinese Felis silvestris catus remains unclear. This study compared the capability of neutralising antibodies in serum against the NB.1 variant prevalent in 2025 with that of the JN.1 variant circulating in 2024 among ill Chinese Felis silvestris catus, and determined whether they could be infected with SARS-CoV-2 variants.

Methods: A total of 392 serum samples from ill cats were subjected to enzyme-linked immunosorbent assay (ELISA) to detect the concentration of total antibodies against the receptor-binding domain of SARS-CoV-2; 40 serum samples screened positive by ELISA were subjected to pseudovirus neutralisation test to detect the titres of neutralising antibodies against the JN.1 and NB.1 variants, and 132 throat swab samples from ill cats were screened using specific reverse transcription polymerase chain reaction.

Results: The geometric mean neutralising titres against the total, NB.1, and JN.1 Omicron variants were 9.51 (95% confidence interval: 7.34-12.3), 24.26 (18.84-31.23), and 48.79 (36.51-65.21) among 40 serum samples from ill cats, respectively. Therefore, neutralisation assays against JN.1 and NB.1 indicated 5.1- and 2.6-fold reductions in neutralising antibody titres, respectively, compared with the total antibody. Additionally, NB.1 showed a 2.91-fold reduction in neutralising antibody titres compared with JN.1. None of the throat swabs from the 132 ill cats were found to be infected with SARS-CoV-2 variants.

Conclusions: NB.1 showed increased immune escape capacity in serum compared with JN.1 among Chinese Felis silvestris catus, suggesting that researchers should include the NB.1 antigen in COVID-19 vaccine candidates.

The mucosal barrier, as a critical interface of the body's defense system, is central to the pathogenesis of allergic diseases, with its structural integrity (epithelial cells, tight junctions, mucus layer, basement membrane) and functional homeostasis being key factors. This paper systematically elucidates the dynamic regulatory network constituted by five major signaling pathways: Wnt/β-catenin, TGF-β/Smad, RhoA/ROCK, MAPK, and JAK-STAT. These pathways interact through cross-talk (for example, Smad7 inhibits TGF-βRI to enhance Wnt signaling, and the β-catenin/Smad4 complex synergistically activates EMT genes), forming synergistic/antagonistic effects that jointly regulate epithelial repair, the expression of tight junction proteins (ZO-1/Claudin/Occludin), mucus secretion (MUC2/MUC5AC), and basement membrane remodeling. In allergic diseases, this network exhibits organ-specific imbalances: respiratory barrier damage is primarily characterized by RhoA/ROCK-mediated abnormal mucus secretion (asthma) and JAK-STAT-driven Th2 inflammation (rhinitis), whereas the intestinal barrier relies more on the epithelial regenerative capacity of the Wnt pathway.We innovatively propose a "phased-organ-targeting strategy": during the acute inflammatory phase (0-72 hours), JAK inhibitors (such as CYT387 nasal spray) are utilized to block STAT6 phosphorylation and control the immune storm; in the repair phase (72 hours to 2 weeks), Wnt agonists (WNT2b-pH microspheres) are employed to promote epithelial regeneration, or RhoA regulators (fasudil inhalation) are used to reconstruct the mucus layer; in the chronic remodeling phase, a temporally regulated dual-pathway therapy (such as JAK-STAT inhibition combined with Wnt activation hydrogels) is applied. The current challenges lie in overcoming pathway redundancy, tissue delivery efficiency, and individual differences in microbial flora. Future efforts should focus on achieving precise interventions through local delivery using nanocarriers, temporally coordinated dosing regimens, and predictive models of microbiota-host interactions.

Autophagy is a conserved cellular process that mediates degradation of damaged organelles, misfolded proteins, and invading pathogens, playing critical roles in intracellular homeostasis and immune regulation. Given that over 70% of infectious diseases and 60% of emerging infectious diseases are zoonotic, posing a major threat to global health, this review aims to summarize the cellular and molecular mechanisms underlying the crosstalk between autophagy and key zoonotic pathogens. We comprehensively retrieved relevant research literature from the PubMed, Web of Science, and Scopus databases (with the retrieval deadline set as December 2025), using core keywords including autophagy, zoonoses, and pathogen-host interactions. The inclusion criteria were original studies and high-quality reviews focusing on molecular mechanisms or clinical translational potential. Finally, a total of 216 core literatures were included for comprehensive analysis. This review is a narrative overview with comprehensive coverage, aiming to systematically summarize the research progress of autophagy in zoonoses, rather than a systematic meta-analysis strictly adhering to the PRISMA guidelines. Key findings include (1): Autophagy can restrict the replication of zoonotic pathogens such as influenza virus and Brucella by mediating their degradation; (2) Some pathogens have evolved strategies to hijack or inhibit autophagy for survival; (3) Several autophagy-related molecules (e.g., ATG5, Beclin-1) have been identified as potential targets for zoonoses prevention and treatment. This review highlights the dual role of autophagy in zoonotic infections and its potential as a therapeutic target. However, further studies are needed to clarify species-specific differences in autophagy regulation and develop targeted interventions. These insights may provide new avenues for the prevention and treatment of severe zoonotic diseases.

Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and systemic inflammation, with accumulating evidence implicating gut microbiota dysbiosis as a key modulator of disease pathogenesis via the gut-lung axis. This review synthesizes current knowledge on the bidirectional communication between the gut and lungs, highlighting how microbial metabolites-particularly short-chain fatty acids (SCFAs), tryptophan derivatives, and bile acids-regulate pulmonary immunity through G-protein-coupled receptors, histone deacetylase inhibition, and aryl hydrocarbon receptor signaling. Dysbiosis-driven disruptions in these pathways exacerbate neutrophilic inflammation, impair regulatory T-cell function, and sustain TLR4/NF-κB activation, amplifying lung tissue damage and remodeling. Therapeutic strategies targeting the gut-lung axis show promise in restoring microbial homeostasis and mitigating COPD progression. Probiotics (e.g., Lactobacillus and Bifidobacterium), prebiotics (e.g., inulin), and dietary interventions (e.g., high-fiber diets) enhance SCFA production, strengthen epithelial barriers, and suppress pro-inflammatory cytokines. Advanced approaches, including fecal microbiota transplantation, nanotechnology-enabled metabolite delivery (e.g., dendrimer-complexed indole-3-acetic acid), and traditional Chinese medicine (TCM) formulations (e.g., the postbiotic formulation Qipian), demonstrate efficacy in preclinical and clinical studies by synchronizing gut-lung microbiota and inhibiting inflammatory pathways. Despite these advances, challenges remain in translating findings to clinical practice, including methodological heterogeneity, antibiotic and corticosteroid confounding, and inter-individual microbiota variability. Future research must integrate multi-omics technologies, validate biomarkers (e.g., Bacteroidales/Lactobacillus ratio, SCFA levels), and develop personalized interventions to bridge the bench-to-bedside gap. Harnessing the gut-lung axis offers transformative potential for COPD management, shifting the paradigm from symptomatic treatment to disease-modifying strategies rooted in microbiome immunology.

Background: Neurodegenerative diseases (NDs) such Alzheimer's disease (AD) and Parkinson's disease (PD) are increasingly understood as systemic disorders driven by chronic neuroimmune dysregulation. The bidirectional communication between the central nervous system (CNS) and peripheral immune compartments is termed neuroimmune crosstalk, plays a pivotal role in disease initiation, progression, and therapeutic resistance. However, mammalian models often obscure mechanistic resolution due to immune redundancy and adaptive complexity.

Objective: This review highlights Drosophila melanogaster as a genetically tractable and evolutionarily conserved model for dissecting innate immune signaling and inter-organ communication in neurodegeneration. We emphasize its utility in resolving causality, identifying conserved cytokine pathways, and modeling systemic inflammation relevant to Parkinson's and Alzheimer's disease.

Key findings: Drosophila possesses a tripartite immune system that is brain-resident glia, circulating hemocytes, and the fat body that coordinates responses via Toll, Immune deficiency (Imd), JAK/STAT, and MAPK pathways. Glial cells engage in Draper-mediated phagocytosis and NF-κB/Relish signaling, while peripheral immune components modulate CNS integrity through cytokines such as Unpaired 3 (Upd3) and Eiger. Furthermore, hyperactivation of the Imd pathway's NF-κB homolog, Relish, within the CNS drives neurodegeneration via the neurotoxic effects of Antimicrobial Peptides (AMPs). These mechanisms mirror mammalian neuroimmune dynamics and reveal conserved therapeutic targets.

Conclusion: Drosophila melanogaster offers unparalleled mechanistic clarity in modeling neuroimmune interactions. Its simplified immune architecture, precision genetics, and compatibility with multi-omics and AI-assisted phenotyping position it as a strategic complement to vertebrate models. Insights from Drosophila are redefining neurodegeneration as a multi-organ process and accelerating the development of inflammation-targeted therapies for ND.

Background: Spinal cord injury (SCI) is a neurological disease with high morbidity and mortality. Post-SCI muscle atrophy is a cascade response to SCI, and failure to actively prevent its occurrence severely affects patients' mobility and quality of life. Therefore, deeply exploring the correlation between muscle atrophy after SCI and the molecular regulation mechanism is of great significance.

Methods: Download GSE21497 expression profile data from the gene expression omnibus (GEO) database. Perform weighted gene co-expression network analysis (WGCNA) on the obtained differentially expressed genes (DEGs). Subsequently, we performed functional and pathway enrichment analyses of key modules. Construct a protein-protein interaction (PPI) network and screen core genes. Finally, the results were verified by real-time polymerase chain reaction(PCR).

Results: A total of 1007 DEGs were obtained, including 533 upregulated genes and 474 downregulated genes. WGCNA analysis identified 161 turquoise modules of DEGs as key modules related to SCI. Functional enrichment analysis showed that these genes were mainly enriched in negative regulation of cellular process, cytosol, response to organic substance, endpoint system, extracellar region, peroxisome proliferators-activated receptors (PPARs) signaling, adherens junction signaling, and DNA replication signaling pathway.

Conclusions: FOS and CCL2 may be involved in the molecular pathophysiology of muscle atrophy after SCI, serving as potential targets for diagnosis or treatment of SCI-related muscle atrophy.