Frontiers in Immunology最新文献

Polycystic ovary syndrome (PCOS) is a common reproductive, endocrine, and metabolic disorder in women of reproductive age, characterized by hyperandrogenemia, insulin resistance, and ovulatory dysfunction. Autophagy, a key cellular homeostasis mechanism, closely interacts with immune-inflammatory responses to drive PCOS pathogenesis. This review highlights the "liver-adipose-ovary circuit"-a pathological network where the liver, adipose tissue, and ovaries crosstalk via autophagy dysregulation, chronic low-grade inflammation, and metabolic disturbances. Abnormal autophagy in adipose tissue induces insulin resistance and inflammatory cytokine release; hepatic autophagy impairment exacerbates non-alcoholic fatty liver disease (NAFLD) and hyperandrogenemia; ovarian autophagy dysfunction disrupts folliculogenesis. These organ-specific abnormalities form a self-reinforcing cycle that amplifies PCOS phenotypes. Clinical therapies targeting this circuit (e.g., quercetin, metformin) show promise by regulating autophagy, improving insulin sensitivity, and restoring reproductive-metabolic balance. Future research should clarify inter-organ molecular mediators and validate autophagy-targeted strategies to advance personalized PCOS treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third highly pathogenic coronavirus to emerge in humans in recent decades. Although primarily a respiratory virus, SARS-CoV-2 can invade the central nervous system (CNS), leading to severe neurological manifestations such as stroke, encephalopathy, and memory loss. However, the mechanisms by which neural cells control SARS-CoV-2 infection remain poorly understood. Here, we demonstrate that SARS-CoV-2 and its Nucleocapsid (N) and Spike (S) proteins induce classical NLRP3 inflammasome activation in astrocytes. Notably, astrocytes lacking NLRP3 or caspase-1 exhibit higher viral loads, indicating a crucial role of the NLRP3 inflammasome in astrocyte-mediated viral control. Similarly, gasdermin-D (GSDMD)-deficient astrocytes display increased susceptibility to infection, although their LDH release remains unaffected, suggesting that pyroptosis is not required for viral restriction. Instead, GSDMD deficiency leads to markedly reduced IL-1β secretion, and exogenous IL-1β rescues the impaired antiviral response in NLRP3-, caspase-1-, and GSDMD-deficient astrocytes. Our findings reveal that astrocytes autonomously control SARS-CoV-2 infection via the NLRP3-GSDMD-IL-1β axis, underscoring their active role in the neuroimmune response to viral infection.

Background: Neurosyphilis is a disease of the central nervous system (CNS) caused by Treponema pallidum (syphilis spirochete), which usually presents with a variety of nonspecific symptoms and is easily misdiagnosed. Although Treponema pallidum can remain latent after treatment, reactivation may occur in the presence of a compromised or immunosuppressed immune system. This article reports a case of reactivation of neurosyphilis after spinal surgery, with the aim of exploring the possible role of immunosuppression in the process.

Case presentation: The patient was a 75-year-old female admitted to the hospital with persistent bilateral lower extremity pain and weakness and a past history of syphilis that was cured 31 years ago. Upon admission, the patient was diagnosed with an intradural occupying lesion and underwent T9-T10 intradural space-occupying lesion resection. Postoperatively, the patient developed symptoms of neurogenic bladder and paraplegia, and further examination revealed abnormal cerebrospinal fluid suggestive of reactivation of neurosyphilis. Through syphilis antibody testing and cerebrospinal fluid analysis, the diagnosis of neurosyphilis was finally confirmed and antisyphilis treatment was started.

Treatment and outcome: The patient received a 14-day course of intravenous benzylpenicillin, which resulted in significant symptomatic improvement and restoration of most functions at discharge. After 12 months of follow-up, the patient had fully recovered, with a progressive decrease in syphilis antibody titers and no neurosyphilis reactivation.

Conclusions: This case emphasizes the importance of preoperative syphilis antibody screening, especially in elderly patients with a history of syphilis. The immunosuppressed state may contribute to the reactivation of syphilis spirochetes; therefore, it is important to consider this potential risk and take appropriate precautions when performing surgical treatments such as spinal surgery. Penicillin remains the therapeutic agent of choice for neurosyphilis, and early diagnosis and treatment are critical to the patient's prognosis.

Background: Sepsis-associated liver injury (SALI) increases mortality in critically ill patients but lacks targeted treatments. Although the natural compound Paeoniflorin shows anti-inflammatory and immunomodulatory potential, its specific function and mechanism in SALI remain unclear.

Methods: A murine model of polymicrobial sepsis was established using cecal ligation and puncture (CLP). Male C57BL/6 mice were randomly allocated to Sham, CLP, CLP+Paeoniflorin (30, 60, 120 mg/kg), CLP+Paeoniflorin+TLR4 agonist (RS09 TFA), and Paeoniflorin-only control groups. Liver injury was assessed through serum ALT/AST measurements, histopathological evaluation, and TUNEL apoptosis assay. Hepatic inflammatory cytokine expression was quantified by qPCR. Macrophage polarization was analyzed via immunohistochemistry for F4/80, CD86 (M1), and CD206 (M2) markers. TLR4/NF-κB pathway activity was examined using Western blotting and immunohistochemistry. Transcriptomic profiling was performed through RNA sequencing and KEGG pathway analysis.

Results: Paeoniflorin administration significantly attenuated CLP-induced elevations in serum ALT and AST levels in a dose-dependent manner, ameliorated histopathological liver damage, and reduced hepatocyte apoptosis. Treatment with Paeoniflorin substantially downregulated hepatic mRNA expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β). Immunohistochemical analysis revealed that Paeoniflorin treatment was associated with a shift in macrophage marker expression, characterized by a reduction in cells co-staining for F4/80 and the classic M1 marker CD86, and an increase in cells co-staining for F4/80 and the classic M2 marker CD206. This suggests a potential modulation of macrophage polarization balance towards an anti-inflammatory phenotype. Both transcriptomic and protein analyses confirmed that Paeoniflorin suppressed activation of the TLR4/NF-κB signaling pathway. The protective effects of Paeoniflorin were completely abolished by co-administration of the TLR4 agonist RS09 TFA.

Conclusion: Paeoniflorin confers protection against sepsis-induced liver injury by modulating macrophage polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype through inhibition of the TLR4/NF-κB signaling pathway. These findings identify Paeoniflorin as a promising candidate for further development as an immunomodulatory therapy for SALI.

Background: The use of molecular allergens have greatly improved the clinical relevance of specific IgE serologies during allergy work-up. Very little is known regarding the added value of molecular allergens in the results of the basophil activation test (BAT).

Objective: To study the BAT concordance when using similar amounts of molecular allergens against source extracts, and to assess factors associated with BAT discrepancies between extract and related component.

Methods: Systematic retrospective monocentric study of all BAT performed at the Trousseau Hospital, Paris, France, with both molecular components and corresponding extract.

Results: Data from 213 interpretable extract/component BAT pairs (89 cow milk, 70 wheat, 28 house dust mites (HDM), 12 peanut, 9 hen egg, 3 peach, 1 apple, 1 chicken meat), corresponding to 150 blood samples from 109 patients were analyzed. Among BAT pairs showing allergen sensitizations, the two reagents only showed moderate agreement (κ = 0.62), with 18% (36/201) discordant BAT results. Among 36 cases of discrepant BAT results between extract and molecular component, 69% (25/36) were extract⁺/component^- (p=0.03), in line with genuine allergic status, in contrast with the opposite case. Even in extract⁺/component⁺ concordant cases, component-stimulated basophils showed 6% less activation rates than their extract-stimulated counterpart. After stratification by allergen, better performances were confirmed with cow milk extract, but not with other allergens, which display large disparity regarding the propensity of different molecular component to activate basophils. Independently of the considered allergen, other variables such as total IgE, BAT positive control values, and treatment with monoclonal antibody or allergen-specific immunotherapy, appear to further modulate the risk of presenting a discordant BAT result.

Conclusion: In our study population, molecular components had lower capacity than the corresponding extract to activate IgE-sensitized basophils, which partly explain higher rates of true positive extract⁺/component^- BAT. Component-based BAT can potentially lead to false-negative results, and extract-based should generally be preferred, especially for cow milk.

Background: Severe community-acquired pneumonia (SCAP) is a significant global health challenge due to its high mortality. Despite advances, early diagnosis and effective management remain critical. Tools like radiomics analyze imaging data for risk assessment, while machine learning and nomograms aid in personalized treatment. Large language models (LLMs) enhance clinical decision-making by analyzing data and supporting care strategies. This study integrates these methods to predict 28-day mortality in SCAP patients.

Methods: A cohort of 599 patients diagnosed with severe community-acquired pneumonia (SCAP), including 316 males and 283 females, from Shanghai East Hospital and Xiamen Humanity Hospital were enrolled in this study. High-resolution lung CT scans were used to segment three-dimensional regions of interest, from which 1,050 radiomic features were extracted. The dataset was divided into a training set (80%) and an independent test set (20%), and k-fold cross-validation was applied to optimize model performance. To address class imbalance, the SMOTE oversampling technique was employed. The study integrated radiomics, nomograms, seven machine learning models, and five LLMs to predict the 28-day mortality risk in SCAP patients. SHAP values were utilized to enhance the interpretability of feature contributions. Not only that, this study integrates the prior knowledge provided by LLMs, processed through an embedding layer, with data-driven feature learning in the main network, and dynamically fuses their outputs using a bias network with a gating mechanism, thereby improving the accuracy and interpretability of LLMs in predicting 28-day mortality risk for SCAP patients.

Results: Key predictors of 28-day mortality included inflammatory markers, cytokines, age, CRP, and oxygenation index. Clinical-Radiomics models achieved strong accuracy (AUC 0.92). Machine learning models, particularly XGBoost (AUC 0.90), were highly effective, with SHAP analysis emphasizing radscore's importance. LLMs like Chatgpt also performed well (AUC 0.78), showcasing the potential of integrating clinical, radiomic, and AI-driven approaches.

Conclusion: This study demonstrates the effectiveness of radiomics, machine learning, and LLMs to predict SCAP outcomes. Models like XGBoost achieved superior accuracy, while SHAP analysis improved interpretability. These advancements highlight the potential for enhanced SCAP prognosis and personalized care strategies.

Tumefactive demyelination is a rare phenotypic subtype of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and poses significant diagnostic challenges due to substantial clinical and radiological overlap with intracranial neoplasms and other demyelinating conditions. This mimicry frequently leads to misdiagnosis and subsequent inappropriate therapeutic interventions and delay in treatment, thereby increasing the risk of adverse clinical outcomes. We present the case of a 31-year-old male with a prior history of MOG-associated optic neuritis (ON) who developed acute-onset dizziness and gait instability evolving over five days. Brain magnetic resonance imaging (MRI) demonstrated an atypical mass-like lesion in the left cerebellar hemisphere with extension to the middle cerebellar peduncle. Serum testing showed MOG-IgG positivity at 1:100 titer (live cell-based assay) with negative AQP4-IgG. Following timely pulse corticosteroid therapy, the patient showed marked symptomatic improvement and received sequential maintenance of oral corticosteroid for six months. A follow-up MRI revealed complete resolution of abnormalities, and no recurrence was observed during the 21-month follow-up period. This case highlights the critical importance of including rare tumefactive MOGAD in the differential diagnosis of mass-like lesions, thereby avoiding the potential morbidity associated with misdiagnosis and delayed treatment. It also underscores the role of maintenance therapy in reducing relapses and preventing disability accumulation.

Background: Vascularized composite allotransplantation (VCA) joins skin, muscle, bone, nerve, and vessels into a single graft that is both highly immunogenic and mechanically complex. Biopolymers, natural or synthetic, can provide structural scaffolding, localized drug release, and immune modulation. Although widely explored in solid-organ transplantation, their utility in VCA is poorly defined. We therefore conducted a systematic review to consolidate current evidence and map translational priorities.

Methods: Adhering to PRISMA 2020 and registered in PROSPERO (CRD420251039845), we searched PubMed, Web of Science, EMBASE, Cochrane Library, and Google Scholar through April 2025. Original studies evaluating biopolymers in any VCA-relevant setting (in vitro, animal, or clinical) were eligible. Clinical quality was judged with the Newcastle-Ottawa Scale and pre-clinical studies with the SYRCLE tool. Given methodological heterogeneity, findings were narratively synthesized.

Results: Eleven studies published between 2014 and 2024 fulfilled inclusion criteria. Collectively, they demonstrate that biopolymers, ranging from decellularized limb and auricular scaffolds to collagen-hydroxyapatite or polycaprolactone bone substitutes, hyaluronic-acid-functionalized vascular grafts, chitosan- or alginate-based drug-eluting coatings, and extracellular-matrix (ECM) sheets delivering cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) with or without rapamycin, consistently enhance vascularization, support multi-tissue regeneration, and preserve mechanical integrity across diverse VCA models. Immunologically, polymer platforms bias host responses toward tolerance: in a murine hind-limb model, ECM combined with CTLA4-Ig and rapamycin extended graft survival to 72 days while promoting pro-regenerative macrophage polarization. Drug-delivery applications also proved effective; calcium-alginate coatings prolonged vancomycin release for up to 50 days in vitro, highlighting the potential for infection control during graft integration. Notwithstanding these benefits, chitosan scaffolds displayed inadequate load-bearing capacity, and heterogeneity in species, graft types, follow-up intervals, and outcome metrics limited direct comparison and impeded meta-analysis.

Conclusion: Biopolymers emerge as potential adaptable platforms that merge mechanical support with finely tuned immune regulation in VCA. Successful translation will depend on tissue-specific material optimization, standardized immunological endpoints, and multicenter studies that replicate clinical complexity. Drawing on lessons from solid-organ transplantation and fostering collaboration among immunologists, biomaterial scientists, and surgeons will be pivotal to moving these technologies from bench to bedside in VCA.