BMC Immunology最新文献

Background and aim: The COVID-19 pandemic has left a lasting imprint on immune function, particularly in the elderly-a population already vulnerable to immunosenescence. While acute and long-COVID immune responses have been widely studied, the long-term apoptotic behavior of peripheral blood mononuclear cells (PBMCs) remains underexplored. This study aims to investigate the legacy of SARS-CoV-2 on PBMC apoptosis in elderly individuals during the post-COVID era, shedding light on potential persistent immune dysregulation.

Materials and methods: In this cross-sectional study, PBMCs were isolated from peripheral blood samples of elderly individuals (> 65 years old) with a documented history of COVID-19 infection at least six months prior. Using multiparametric flow cytometry, we quantified early and late apoptosis markers (Annexin V/PI), mitochondrial membrane potential disruption (ΔΨm), and expression of pro-apoptotic (Bax, Caspase-3) and anti-apoptotic (Bcl-2) proteins. Statistical analyses were performed to assess intergroup differences and correlations with clinical history. This study was conducted in 2025.

Results: Elderly post-COVID individuals exhibited a significantly elevated proportion of apoptotic PBMCs compared to controls (p < 0.01), particularly within the CD4 + and CD8 + T-cell subsets. Mitochondrial depolarization and increased Bax/Bcl-2 ratios indicated a shift toward intrinsic apoptotic pathways. Caspase-3 activation was also heightened in the post-COVID group. Notably, apoptotic burden correlated with time since infection and severity of initial illness.

Discussion: Our findings suggest a prolonged apoptotic signature in the immune cells of elderly individuals following recovery from COVID-19. These alterations may reflect a sustained immune exhaustion or maladaptive remodeling of lymphocyte populations, potentially contributing to impaired immunosurveillance and increased vulnerability to secondary infections or chronic inflammatory conditions.

Conclusion: COVID-19 may cast a long immunological shadow in the elderly, with persistent PBMC apoptosis representing a novel facet of post-viral immune dysregulation. Flow cytometry reveals a unique apoptotic phenotype that could serve as a biomarker for long-term immune health and guide post-pandemic clinical management strategies for aging populations.

The mechanism of epitope mimicry could have implications for the safety of vaccine development. OmpA is one of the most promising antigens of Acinetobacter baumannii. This property convinced us to investigate OmpA's potential to trigger autoimmune responses. To this end, BLAST searches were performed using the OmpA sequence and its overlapping peptides to find identical peptides in the human proteome. These peptides were analyzed for their epitopic and HLA binding properties. The population coverage was then calculated for the peptides. OmpA showed high identity among numerous strains of A. baumannii and had no similar counterparts in the human proteome. Three OmpA peptides (TKNYDSKI, LSLARANS, and GQEAAAPA) shared identity and similarity with human proteins. Amongst, LSLARANS, which was found in Isthmin-1, the one with the highest potential to induce autoimmune responses was identified. LSLARANS was found in a B-cell positive assay of OmpA and acted as an HLA binder (such as HLA-A*03:01). Approximately 18% of the world's population were determined to be more susceptible to probable A. baumannii-post-infection autoimmune disease, which could be rooted in OmpA similarity. Mutation sensitivity analyses indicated that the TKNYDSKI peptide is sensitive to engineering and modification. Given these circumstances, these peptides should be avoided in vaccine design efforts to reduce the risk of autoimmune responses.

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.