BMC Immunology最新文献

Background: T lymphocyte dysfunction is closely associated with immunosuppression in sepsis, whereas the underlying mechanisms are not fully understood.

Results: In this study, we established a mouse model of cecal ligation and puncture (CLP)-induced sepsis and observed immunometabolic alterations in splenic T cells. Serum energy metabolites related to glycolysis and the tricarboxylic acid (TCA) cycle were imbalanced. Splenic T cells from septic mice showed a shift in subset distribution, with decreased naïve T cells and increased effector populations, along with concurrent activation and exhaustion phenotypes. Notably, mitochondrial mass and mitochondrial membrane potential were significantly diminished in both CD4⁺ and CD8⁺ T cell, correlated with increased programmed cell death protein 1 (PD-1) expression. Transmission electron microscopy further confirmed mitochondrial morphological alterations in CLP-derived CD3⁺ T cells. Furthermore, seahorse assays demonstrated impaired metabolic reprogramming capacity in activated CLP splenic CD3⁺ T cells, with suppressed glycolytic and oxidative phosphorylation responses. This impairment was coupled with reduced fold-increases in mitochondrial mass and mitochondrial membrane potential levels upon activation in both CD4⁺ and CD8⁺ T cell compared to controls. Clinically, peripheral T cells from septic patients showed elevated CD69 and PD-1 expression, a significant increase in CD39 and a decrease in CD73, increased mitochondrial mass and decreased mitochondrial membrane potential, particularly in those with septic shock.

Conclusions: Our findings provide several layers of T cell dysfunction in sepsis, linking subset redistribution, an exhausted phenotype, mitochondrial impairment, and reduced proliferative capacity, suggesting that future therapeutic interventions aiming to reverse sepsis-induced immunosuppression may require a combinatorial approach.

Background: Anti-interferon (IFN)-gamma (γ) autoantibody positivity (AIGA) is a rare cause of adult-onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. Due to its rarity, the diagnosis of AIGA is often missed or delayed.

Methods: We used the hospital information system of the First Affiliated Hospital of Wenzhou Medical University to retrospectively analyze the data of patients with AIGA between January 2018 and March 2024. Clinical, laboratory, and outcome data were collected and analyzed.

Results: Six patients with AIGA were included in this study. A retrospective review of the clinical characteristics and laboratory results showed that all patients had recurrent opportunistic infections, and five patients had hypergammaglobulinemia before receiving the diagnosis of AIGA. All six patients presented with pneumonia and recurrent cough; two patients presented with recurrent skin abscesses, two presented with recurrent penile ulcers, and two presented with severe bone destruction. Of these, five patients were infected with Talaromyces marneffei (T. marneffei). After being diagnosed with AIGA, all six patients received routine anti-infection therapy. As the disease progressed, all patients presented with recurrent infections. Notably, five patients exhibited elevated serum immunoglobulin G (IgG) (median 25.06 g/L; interquartile range, 17.73-38.22) during a previous admission. One succumbed to respiratory failure at follow-up, while five survived.

Conclusion: The diagnosis of AIGA is often delayed and should be considered as a differential diagnosis in patients with recurrent opportunistic infections and hypergammaglobulinemia.

Introduction: Asthma is a complex and heterogeneous disease that significantly impacts quality of life. Eosinophilic asthma, characterized by elevated eosinophil levels, leads to inflammation and hypersensitivity. Many patients remain inadequately managed, resulting in frequent exacerbations and hospitalizations despite standard treatment options. Depemokimab, a long-acting monoclonal antibody that targets IL-5, could offer a novel approach for managing severe eosinophilic asthma.

Methods: A systematic search was conducted across the PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and Scopus databases up to January 2025. Dichotomous outcomes were pooled as risk ratios (RR), and continuous outcomes were represented as mean differences (MD) from baselines, with 95% confidence intervals (CIs), using a random-effects model. Statistical analysis was performed using RevMan (version 5.4).

Results: Two randomized controlled trials (n = 762) were included. Depemokimab significantly reduced the annualized rate of exacerbations (MD -0.59, 95% CI [-0.76 to -0.42], P < 0.00001) and improved the St. George's Respiratory Questionnaire (SGRQ) score (MD -2.93, 95% CI [-5.48 to -0.38], P = 0.02). It also significantly decreased the annualized rate of exacerbations requiring hospitalization or emergency department visits (RR 0.33, 95% CI [0.15 to 0.75], P = 0.008). No significant differences were observed in changes to the Asthma Control Questionnaire (ACQ-5) score, pre-bronchodilator FEV1, or asthma-related diaries. Safety outcomes indicated significantly lower risks for pneumonia, nasopharyngitis, rhinitis, and back pain in the Depemokimab group. However, an increased risk of allergic rhinitis was noted (RR 2.71, 95% CI [1.22 to 6.02], P = 0.01). No significant differences were observed in serious adverse events or other adverse events.

Conclusion: Depemokimab demonstrates promising efficacy in reducing clinically significant exacerbations and improving quality of life measures in patients with severe eosinophilic asthma, with a generally favorable safety profile. However, the current evidence is limited to two trials with relatively short follow-up periods. Further research with larger, more diverse patient populations and extended long-term follow-up is needed to establish the drug's definitive place in therapeutic algorithms and to comprehensively evaluate potential long-term safety concerns before widespread clinical implementation can be recommended.

Background: Severe pneumonia (SP) poses a serious threat to patients' lives, and this study aimed to explore the diagnostic and prognostic value of miR-193b-3p on SP, thereby providing novel insights for the clinical management of SP.

Methods: The miR-193b-3p expression was evaluated by PCR. The diagnostic value of miR-193b-3p on SP was assessed by ROC. The association between miR-193b-3p expression and the SP severity was assessed by the correlation analysis. The correlation between miR-193b-3p expression and the survival status of SP patients was evaluated by the Kaplan-Meier survival analysis. Potential independent prognostic factors for SP were predicted by multivariate COX regression analysis. Bioinformatics analysis assessed the possible pathways regulated by miR-193b-3p.

Results: Upregulation of miR-193b-3p in SP patients showed a diagnostic value in SP. The miR-193b-3p expression was positively correlated with the levels of WBC, NEU, CRP, PCT, BNP, and D-D, and negatively correlated with LYM. The expression level of miR-193b-3p was significantly associated with the APACHE-II and CPIS scores, and a better survival rate was observed in SP subjects with low miR-193b-3p expression levels. MiR-193b-3p, together with CRP, PCT, APACHE-II, and CPIS, could also serve as independent prognostic factors for SP. MiR-193b-3p was associated with PI3K-Akt, MAPK, FoxO, TRP channel, and Wnt signaling pathways.

Conclusion: Upregulated miR-193b-3p expression in SP patients had a diagnostic and prognostic value for SP.

Background: Monocyte chemoattractant protein-1 (MCP-1) has been utilized as a prognostic indicator for sepsis patients; however, the findings have been inconsistent. This meta-analysis seeks to elucidate the prognostic significance of MCP-1 in individuals diagnosed with sepsis.

Methods: We systematically queried four databases (Web of Science, PubMed, EMBASE, Cochrane Library) to identify studies published from the establishment of the databases until January 2025. Hazard ratios (HRs) with 95% CIs were employed to evaluate the prognostic significance of MCP-1 in this patient population. In our study, the Newcastle-Ottawa Quality Assessment Scale was evaluated for quality assessment, and Funnel plot was used for publication offset.

Results: A total of 592 patients from eight studies were included in the evaluation. The findings revealed that MCP-1 levels were significantly elevated in non-survivors compared to those who survived [SMD = 0.54, 95% CI: 0.25-0.82, P = 0.0002]. Our study demonstrated that elevated levels of MCP-1 were significantly associated with an unfavorable prognosis in patients with sepsis, with a hazard ratio (HR) of 1.36 (95% confidence interval: 1.25-1.48; P < 0.00001) using a random-effects model. The funnel plot indicated no publication bias.

Conclusion: This meta-analysis suggests that elevated levels of MCP-1 could serve as a valuable prognostic indicator in sepsis patients, however, this conclusion still requires validation through higher-quality studies with longer-term follow-up.

N6-methyladenosine (m6A) modification plays a critical role in lipid metabolism, yet the mechanism by which the m6A demethylase Fat mass and obesity-associated protein (FTO) regulates hepatic steatosis and autophagy remains unclear. This study aimed to investigate whether FTO modulates lipid metabolism and autophagy through m6A-dependent regulation of Beclin-1 (BECN1). In vitro, HepG2 cells were treated with free fatty acids (FFA) to establish a lipid overload model. Lipid levels were measured enzymatically; autophagy markers were assessed by Western blot; m6A modification was evaluated via dot blot, MeRIP, and RIP assays; and RNA stability was determined using actinomycin D. In vivo, high-fat diet (HFD)-fed mice were established. Liver histology and lipid profiles were analyzed. FFA treatment reduced global m6A levels and upregulated FTO expression. FTO knockdown attenuated lipid accumulation, improved dyslipidemia, and restored autophagy in HepG2 cells. Mechanistically, FTO directly bound to BECN1 mRNA and demethylated it at the adenine-567 site, thereby inhibiting its stability and expression. Rescue experiments confirmed that BECN1 knockdown reversed the beneficial effects of FTO silencing on lipid metabolism and autophagy. In HFD-fed mice, hepatic FTO knockdown ameliorated steatosis and improved serum and hepatic lipid levels. In conclusion, FTO deficiency enhances BECN1 m6A methylation and mRNA stability, promoting autophagy and ameliorating lipid accumulation. These findings identify FTO as a potential therapeutic target for treating hyperlipidemia and related metabolic disorders.