BMC Immunology最新文献

Background: Drug-resistant Streptococcus pneumoniae (SP) infections pose a significant global health threat, with a limited availability of effective treatments to prevent disease progression. Chlorogenic acid (CGA) exhibits potent antioxidant and antimicrobial properties, though its exact mechanisms in combating bacterial infections remain not yet fully elucidated. Pneumolysin (PLY), a pivotal virulence factor of SP, specifically contributes to the pathogenesis of these infections.

Purpose: This study aimed to investigate the role of SP-derived PLY in triggering macrophage ferroptosis and to elucidate the potential mechanism underlying CGA-mediated regulation of this process.

Methods: A macrophage-SP co-culture model was established to investigate PLY-induced ferroptosis and the mechanisms underlining CGA-mediated antimicrobial effects. Hemolysis assays were conducted to assess PLY activity, and macrophage apoptosis was evaluated using an Annexin V/PI apoptosis detection kit and CCK-8 assay. Key biomarkers, including intracellular ROS levels, mitochondrial membrane potential, MDA content, and total iron levels, were measured using commercial assay kits. Transmission electron microscopy (TEM) was utilized to analyze mitochondrial ultrastructural alterations, particularly morphological changes in the mitochondrial membrane and cristae. Additionally, the expression of key ferroptosis-related factors was analyzed via qRT-PCR, Western blotting, and immunofluorescence staining to delineate the underlying molecular pathways.

Results: CGA markedly suppressed SP proliferation and attenuated PLY activity. Co-culture with SP or PLY exposure significantly decreased macrophage viability and triggered apoptotic cell death, whereas CGA treatment markedly attenuated apoptosis. CGA upregulated the expression of Nrf2, SOD1, and HO-1 while substantially decreasing intracellular ROS accumulation. Additionally, CGA preserved mitochondrial membrane integrity and significantly lowered MDA content and total iron levels in macrophages. Furthermore, CGA significantly upregulated the expression of key ferroptosis-related factors, including GPX4 and SLC7A11.

Conclusions: CGA effectively attenuates SP-induced macrophage ferroptosis by activating the Nrf2/GPX4 signaling axis. Notably, PLY was identified as a critical mediator of SP-induced macrophage ferroptosis, and further investigations are warranted to elucidate the exact molecular mechanisms.

Objective: The present study aimed to explore the distribution patterns of IgE characteristics and peripheral blood inflammatory markers in pediatric patients with allergic reactions.

Methods: Patients' data were collected, including age, gender, and peripheral blood parameters, including white blood cells (WBC), neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), red blood cells (RBC), and platelets (PLT). Serum total Immunoglobulin E (tIgE) assays were performed using a fully automated specific protein analysis system, and specific Immunoglobulin E (sIgE) was detected through the AllergyScreen assay. The clinical data of these patients were retrospectively analyzed.

Results: A total of 405 samples were included in the study, including 335 patients and 70 normal controls. Our study reveals that aeroallergens are the main cause of allergic reactions in children, and 26.3% of sensitized pediatric subjects exhibit atypical immunological profiles characterized by non-elevated tIgE expressions and low sIgE sensitization. Notably, the Eosinophil-to-Lymphocyte Ratio (ELR) demonstrates significant predictive value for IgE pattern and exhibits a positive correlation (p < 0.001) with tIgE sensitization intensity.

Conclusion: These findings position ELR as a promising peripheral blood inflammatory biomarker for assessing the risk of anaphylaxis in pediatric patients with both tIgE and sIgE elevation.

Background: Inborn errors of immunity (IEI) are inherited defects of innate or adaptive immune system. Thrombocytopenia is a significant multifactorial complication in IEI patients leading to severe clinical consequences including coagulative disorders and vasculopathies.

Methods: In the present study, we assessed frequency of thrombocytopenia in the most common IEI including combined immunodeficiency (CID), common variable immunodeficiency (CVID), selective immunoglobulin A deficiency (SIgAD), agammaglobulinemia (AGA), hyper immunoglobulin M (HIGM) syndrome, chronic granulomatous disease (CGD) and congenital neutropenia (CN). Also, we compared demographic, clinical and laboratory data between IEI patients with and without thrombocytopenia.

Results: A total of 890 patients (37% female) were included in this study. The frequency of thrombocytopenia in total IEI was 26.6%. Patients with CID and SIgAD had the highest and lowest frequency of thrombocytopenia (50.9% and 8.7%), respectively. Although rare, thrombocytopenia was more severe (< 50000/ul) among patients with AGA compared to other IEI entities. Notably hepatosplenomegaly and autoimmunity were significantly associated with thrombocytopenia and higher mortality in patients with humoral immunodeficiencies.

Conclusion: The significant association between thrombocytopenia with lymphoproliferation and autoimmunity emphasizes the importance of paying attention to these clinical features for suspecting IEI disorders. Understanding the pathophysiology of thrombocytopenia in various genetic defects associated with IEI is required for the development of proper diagnostic and therapeutic techniques as well as improved quality of life of these patients.

Background: PD-1/PD-L1 inhibitors have revolutionized urothelial carcinoma (UC) treatment; however, the effects of prior or concurrent therapies on PD-L1 regulation remain unclear. This study investigates whether enfortumab vedotin (EV), a nectin-4-targeting antibody-drug conjugate, modulates PD-L1 expression in UC cells, and explores the underlying molecular pathways.

Methods: UC cell lines RT4 (high nectin-4 expression) and T24 (low nectin-4 expression) were treated with EV (10 µg/ml) for 6, 12, or 24 h, followed by a 48-hour drug-free period. Protein and mRNA expression levels of PD-L1, NF-κB, and STAT3 were quantified using western blotting and qRT-PCR.

Results: EV treatment upregulated PD-L1, NF-κB, and STAT3 in a time-dependent manner, with a more pronounced effect observed in RT4 than in T24 cells. PD-L1 protein levels increased 0.761-fold (12 h) and 2.399-fold (24 h) in RT4, whereas T24 showed a decrease (0.517-fold at 12 h) or minimal change (0.006-fold at 24 h). NF-κB expression increased 64.42-fold (12 h) and 97.03-fold (24 h) in RT4, compared to 1.251-fold (12 h) and 1.210-fold (24 h) in T24. STAT3 levels rose 2.334-fold (12 h) and 2.844-fold (24 h) in RT4, whereas T24 showed increases of 1.620-fold (12 h) and 1.379-fold (24 h). At the mRNA level (6 h post-treatment), PD-L1, NF-κB, and STAT3 were upregulated by 1.228-, 1.332-, and 1.225-fold, respectively, in RT4 cells.

Conclusion: EV is associated with increased PD-L1 expression, along with upregulation of NF-κB and STAT3, suggesting a mechanistic link that may contribute to immune modulation in nectin-4-high bladder cancer cells. These findings highlight the need for combination strategies integrating EV with PD-1/PD-L1 inhibitors to optimize therapeutic outcomes in UC.

Background: Chronic low-grade inflammation is often seen in individuals with insulin resistance, characterised by increased levels of pro-inflammatory cytokines, such as TNF-α (tumour necrosis factor-alpha) and IL-6 (interleukin-6). Insulin resistance (IR) and vitamin D deficiency are increasingly recognised as interconnected metabolic issues. Research indicated that low vitamin D levels may impair insulin sensitivity, while insulin resistance can worsen vitamin D deficiency, creating a vicious cycle. This study aims to explore the relationship between TNF-α and IL-6 expression levels and vitamin D levels in insulin-resistant patients with type 2 diabetes mellitus (DM), and compare them with non-diabetic controls to better understand the role of vitamin D in inflammation, disease development, and progression.

Methods: From a total of 150 participants, 30 were healthy individuals (the control group), and 120 were patients with type II diabetes. The current case-control study compared TNF-α, IL-6 expression levels, and serum vitamin D levels between insulin-resistant patients and non-diabetic controls.

Results: The demographic and clinical variables were statistically significant. The case-to-control ratio was 4:1. Higher levels of TNF-α and IL-6 were found in DM patients compared to non-diabetic controls. Insulin-resistant patients exhibited higher IL-6 levels (5.47 ± 0.30 pg/ml) than healthy participants (2.64 ± 0.83 pg/ml), with p-value < 0.001. Vitamin D levels were significantly lower in DM patients (22.33 ± 11.43 ng/ml) compared to healthy subjects (34.12 ± 2.08 ng/ml), with p-value < 0.001. TNF-α levels were also significantly higher in DM patients (7.99 ± 0.35 pg/ml) (p-value < 0.001) than in the healthy group (4.24 ± 0.27 pg/ml). Using qPCR and measuring disease severity, the relationship between cytokine gene expression and insulin resistance was assessed. The positive associations between TNF-α, IL-6, vitamin D deficiency, poor glycaemic control, and other disease conditions reflect a fundamental pathophysiological mechanism in insulin resistance in DM patients. This ultimately leads to increased inflammation and tissue damage, worsening the complications of diabetes.

Background: Malaria, a prevalent disease in Sudan, has a significant impact on socioeconomic conditions. Cytokines play a crucial role in regulating the immune response during infectious diseases. This study investigates the interplay between malaria and immune response modulation in the River Nile State, focusing on tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), transforming growth factor-beta1 (TGF-β1), and interleukin-10 (IL-10).

Method: Ninety participants with microscopy-confirmed malaria were enrolled. Parasite density and COVID-19 co-infection were assessed. Cytokine levels were measured using ELISA.

Results: TNF-α, IFN-γ, and TGF-β1 levels were significantly associated with parasite density (P < 0.05), but not IL-10. TGF-β1 was significantly higher in P. vivax infections, while IL-10 was elevated in P. falciparum cases. Uric acid levels were lower in participants co-infected with COVID-19 (P < 0.05).

Conclusion: The study's findings show how cytokines affect the immune response, impacting both parasite clearance. TNF-α, IFN-γ, and TGF-β1 are positively linked to parasite density (r = 0.42, 0.38, 0.51; P < 0.01). IL-10 levels were higher in P. falciparum compared to P. vivax (560.0 vs. 415.6 pg/mL, P = 0.019).

This study investigates the protective effects and underlying mechanisms of curcumin in sepsis-associated acute kidney injury (SA-AKI). Using a cecal ligation and puncture (CLP) model to simulate SA-AKI, our results demonstrate that curcumin significantly reduced serum creatinine and urea nitrogen levels, alleviated tubular damage and inflammation, improved cellular activity, and inhibited apoptosis. Further analysis revealed that curcumin inhibited the expression of p300 and decreased protein lactylation modification in renal tissue, thereby exerting anti-inflammatory and antioxidant effects. These findings suggest that curcumin may have potential therapeutic value for the prevention and treatment of SA-AKI.