BMC Immunology最新文献

Objective: Our research aimed to clarify the roles of M1 and M2 macrophages in leprosy, focusing on their polarization states, phagocytic capacities, and the survival of M. leprae within these macrophage subsets.

Methods: M1-like macrophages were induced by IFN-γ, IL-4 induced M2-like macrophages, and then they were compared with M. leprae-induced macrophages regarding cell-surface antigen expression and cytokine secretion. The phagocytic capabilities of M1-like and M2-like cells were assessed using a laser-scanning confocal microscope. Simultaneously, their bactericidal capacities were evaluated by 16S rRNA/RLEP qPCR to determine the viability of M. leprae.

Results: M1-like macrophages induced by IFN-γ were characterized by CD86 and CD68 expression and an elevated expression of the IRF-5 gene. In contrast, M2-like macrophages induced by IL-4 were distinguished by enhanced expression of CD163 and CD206 markers and the upregulation of the IRF-4 gene. M. leprae-induced macrophages encompass CD86⁺CD68⁺(M1 markers ) and CD163⁺CD206⁺( M2 markers ) subpopulations, potentially displaying characteristics of both M1-like and M2-like phenotypes. M1-like macrophages secreted Th1 cytokines, including IL-1β, IL-6, IL-15, and TNF-α, whereas M2-like macrophages secreted IL-10 and TGF-β. At different stages, macrophages induced by M. leprae released Th1 and Th2 cytokines. The phagocytic ability of M2-like macrophages exceeded that of M1-like macrophages. Nevertheless, M. leprae viability was notably higher in M2-like macrophages, indicating a weaker sterilizing capacity than in M1-like macrophages. Conversely, M1-like macrophages demonstrated potent bactericidal activity, although their phagocytic ability was relatively lower than that of M2-like macrophages.

Conclusion: Our findings suggested the notable significance of macrophage polarization in leprosy. M1 macrophages exhibited a relatively strong bactericidal effect against M. leprae, while M2 macrophages might have been somewhat associated with pathogen persistence.

Background: Oral Lichen Planus (OLP) is classified by the World Health Organization as an Oral Potentially Malignant Disorder (OPMD). OLP is characterized by chronic inflammation, which may contribute to its malignant transformation. In this study, we examined whether Interferon Regulator Factor 6 (IRF6), a key regulator of immune responses and epithelial homeostasis, modulates inflammation in oral keratinocytes via Toll-Like Receptor 2 (TLR2). This regulation may contribute to the malignant transformation of OLP.

Methods: Primary Human Oral Keratinocytes (HOKs) were exposed to lipopolysaccharide (LPS) and fibroblast-stimulating lipoprotein (FSL-1) to activate TLR signaling. To assess the transcriptional and post-transcriptional effects of IRF6, HOKs were transfected with constructs expressing wild-type IRF6, a C-terminal phosphomimic variant (hIRF6-DDD), or a phospho-inhibitory variant (hIRF6-AAA). RT-qPCR was performed to evaluate gene expression of TLR signaling components and immuno-cytochemistry (ICC) was used to assess the localization of cell adhesion proteins.

Results: Our results indicate that, in HOKs, the phosphorylation state of the IRF6 C-terminus modulates adherens junctions, influences IRAK1 colocalization, and regulates CCL5 expression-a chemokine essential for T-cell recruitment in epithelial tissue.

Conclusions: These findings suggest that post-translational modification of IRF6 is a key regulator of immune homeostasis in the oral epithelium, priming epithelial cells to initiate an immune response upon loss of epithelial integrity and bacterial adhesion.

Background: Multiple myeloma (MM) is a malignant plasma cell tumor. Regulatory T cells (Tregs), key components of the immunosuppressive tumor immune microenvironment (TIME), play a significant role in MM progression. One mechanism of anti-MM activity of anti-CD38 monoclonal antibodies is reducing CD38⁺ Tregs. Cyanidin-3-O-glucoside (C3G), a natural CD38 inhibitor, effectively suppresses enzymatic activity of CD38. Consequently, we investigated whether C3G could serve as a novel therapeutic agent for MM by targeting Tregs.

Methods: A MM-bearing mouse model was established and treated with C3G to investigate whether C3G can modulate the TIME for therapeutic effects. Tumor growth was monitored, and changes in peripheral blood lymphocyte subsets were assessed to evaluate the immune-modulating effects of C3G. In addition to that, C3G was applied to Naive CD4⁺ T cells derived from the peripheral blood of healthy individuals in vitro to verify its impact on level of Tregs. Network pharmacology and RNA sequencing (RNA-seq) were employed to explore the potential mechanisms by which C3G targets Tregs, and validation was performed using real-time PCR.

Results: C3G demonstrated therapeutic effects in MM-bearing mice, reducing the proportion of Tregs in peripheral blood while showing no significant effects on T cells, B cells, or NK cells. In vitro studies revealed that C3G's effects on Tregs were concentration-dependent and capable of reducing Tregs even in the presence of MM cells. Integration of network pharmacology and RNA-seq results suggested that downregulation of granzyme B (GZMB) and upregulation of heme oxygenase 1 (HMOX1) at the transcriptional level are key mechanisms by which C3G influences Tregs.

Conclusion: C3G exerts therapeutic effects on MM by reducing the proportion of Tregs and thereby restoring anti-tumor immunity. The mechanism may be related to the decrease of GZMB level mediated by the inhibition of CD38.

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.