BMC Immunology最新文献

Mycobacterium tuberculosis (M. tuberculosis, Mtb) is a pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of most cases of tuberculosis. Macrophages play essential roles in defense against invading pathogens, including M. tuberculosis. The study of M. tuberculosis-associated antigens is one of the hotspots of current research. The secreted proteins of M. tuberculosis, including early secretory antigen target 6 (ESTA6) and culture filtrate protein 10 (CFP-10), are crucial for the immunological diagnosis of tuberculosis. However, the relationship of CFP-10 alone with macrophages is still not well understood. In the present study, we report that the purified recombinant protein CFP-10 (rCFP-10) significantly enhanced the phagocytic capacity of murine macrophages. rCFP-10 induces both TNF-α and IL-6 production. Additionally, RNASeq analysis revealed that rCFP10 triggers multiple pathways involved with macrophage activation. Interestingly, neither mitochondrial reactive oxygen species nor lysosomal content had a significant difference treated with rCFP-10 in macrophages. Moreover, inhibition of the mammalian target of rapamycin (mTOR) activity was shown to significantly reverse the rCFP10-induced phagocytosis, various genes involved in lysosome acidification and TLR signaling. These findings highlight that the CFP-10 plays an essential role in the invasion of macrophages by M. tuberculosis, which is partly regulated by the mTORC2 signal pathway.

Background: This study utilizes the FDA Adverse Event Reporting System (FAERS) database to compare the adverse reaction signals of cyclosporine and tacrolimus, two widely used immunosuppressants, in relation to drug-induced kidney injury. The findings aim to inform clinical decision-making.

Methods: The study retrospectively analyzed data from January 2004 to September 2024, employing both frequency analysis and Bayesian methods. We assessed and compared the mortality rates, hospitalization rates, and the association of cyclosporine and tacrolimus with kidney injury to elucidate the renal toxicity of these two drugs.

Results: After data processing, we identified a total of 3,449 cyclosporine-related kidney injury reports and 5,538 tacrolimus-related kidney injury reports. The results revealed a stronger association between tacrolimus and kidney injury. Additionally, kidney injuries associated with both cyclosporine and tacrolimus predominantly affected males. Furthermore, the hospitalization rate for cyclosporine-related kidney injury was 34.40%, compared to 44.50% for tacrolimus. The mortality rate associated with cyclosporine-induced kidney injury was higher than that of tacrolimus.

Conclusion: This study utilized the FDA Adverse Event Reporting System (FAERS) database from January 2004 to September 2024 to perform a comprehensive analysis of adverse drug-related kidney injury reactions to cyclosporine and tacrolimus. The results suggest that both cyclosporine and tacrolimus are associated with renal injury, but tacrolimus appears to reduce mortality while increasing hospitalization rates. This serves as a critical warning for planning future treatment regimens, drug monitoring, and reducing adverse effects.

This review comprehensively explores the intricate immune responses within the oral cavity, emphasizing the pivotal role of saliva in maintaining both oral and systemic health. Saliva, a complex biofluid, functions as a dynamic barrier against pathogens, housing diverse cellular components including epithelial cells, neutrophils, monocytes, dendritic cells, and lymphocytes, which collectively contribute to robust innate and adaptive immune responses. It acts as a physical and immunological barrier, providing the first line of defense against pathogens. The multifaceted protective mechanisms of salivary proteins, cytokines, and immunoglobulins, particularly secretory IgA (SIgA), are elucidated. We explore the natural and induced immune responses in saliva, focusing on its cellular and molecular composition. In addition to saliva, we highlight the significance of a serum-like fluid, the gingival crevicular fluid (GCF), in periodontal health and disease, and its potential as a diagnostic tool. Additionally, the review delves into the impact of diseases such as periodontitis, oral cancer, type 2 diabetes, and lupus on salivary immune responses, highlighting the potential of saliva as a non-invasive diagnostic tool for both oral and systemic conditions. We describe how oral tissue and the biofluid responds to diseases, including considerations to periodontal tissue health and in disease periodontitis. By examining the interplay between oral and systemic health through the oral-systemic axis, this review underscores the significance of salivary immune mechanisms in overall well-being and disease pathogenesis, emphasizing the importance of salivary mechanisms across the body.

Immune-checkpoint inhibitors (ICIs) can cause inflammation and immune-related adverse events (irAEs). Although irAEs may be caused by dysregulation of cytokines, the impact of various COVID- 19-related factors on expression of ICI-related AEs remains unclear. Assessment of AEs following ICI administration during the COVID- 19 pandemic may provide valuable insights that enable optimization of patient selection, thereby maximizing the benefits of ICI therapy. The aim of this study was to investigate the actual occurrence of severe AEs after ICI administration during the COVID- 19 pandemic. The medical records of patients who received ICI at Saga University Hospital were examined retrospectively. The primary endpoint was the incidence of all AEs ≥ Grade 3 that occurred after ICI administration. The survey period, from Jan 2020 to Dec 2022, was divided into an earlier (Jan 2020-March 2021) and a later (April 2021-Dec 2022) period. AEs with a clear cause other than ICI were excluded from the analysis. A total of 527 patients were included in the analysis, with a median follow-up of 422 days. During the COVID- 19 pandemic, the incidence of AEs ≥ Grade 3 after ICI administration was 52.8%. The incidence of AEs ≥ Grade 3 AEs after ICI administration was significantly higher during the later period [23.4% (57/244) in the earlier period and 49.8% (236/474) in the later period; mixed effect model p < 0.0001, odds ratio, 3.37 (95% CI: 2.32-4.89)]. Overall survival was significantly worse in the group with AEs ≥ Grade 3 than in the group without AEs ≥ Grade 3 [HR (95% CI) = 0.48 (0.36-0.65), p = 0.0001]. During the COVID- 19 pandemic, it became clear that the incidence of severe AEs (including irAEs) increased after ICI administration, particularly during the later period of the disease. Various factors may be associated with occurrence of severe AEs after ICI administration, and long-term careful observation and prospective multicenter clinical studies are required.

Background: Sepsis, characterized by high morbidity and mortality, necessitates the identification of novel diagnostic and prognostic biomarkers to enhance patient outcomes. Prior research has highlighted the potential clinical utility of long non-coding RNAs (lncRNAs) in sepsis. This study aimed to investigate the clinical significance and underlying mechanisms of serum lncRNA Cytochrome P450 family 1 subfamily B member 1 antisense RNA 1 (CYP1B1-AS1) expression in sepsis.

Methods: Differentially expressed lncRNAs in sepsis patients were explored via GEO database. Sepsis patients and Control subjects were included. An in vitro cellular model was established with LPS-stimulated THP- 1 cells. RT-qPCR assessed CYP1B1-AS1 and miR- 18a- 5p expression. ROC analysis evaluated diagnostic and predictive value. Kaplan-Meier curves and Cox regression analyzed the prognostic value of CYP1B1-AS1. Flow cytometry and ELISA assessed cell apoptosis and inflammatory factors levels. Dual luciferase reporter, RIP, and RNA pull down to validate target binding relationship.

Results: The GSE217700 database shows that CYP1B1-AS1 was upregulated in sepsis. Serum levels of CYP1B1-AS1 were higher in sepsis patients than controls. CYP1B1-AS1 was positively correlated with SOFA and APACHE II scores and distinguished sepsis patients from controls. The 28-day mortality rate for sepsis patients was 29.31%. High CYP1B1-AS1 expression in sepsis patients predicts a worse prognosis and is a potential risk factor. CYP1B1-AS1 targets miR- 18a- 5p. Silencing CYP1B1-AS1 reduced LPS-inducted apoptosis and inflammatory factor promotion, which the miR- 18a- 5p inhibitor reversed.

Conclusion: CYP1B1-AS1 serves as a biomarker for sepsis diagnosis and poor prognosis, potentially promoting inflammation and apoptosis by targeting miR- 18a- 5p.

Background: Severe pneumonia is an important contributor to the high mortality of sick young children. The microRNA-125b-5p (miR-125b-5p), which is widely involved in various cancers, is closely related to a variety of lung diseases. However, its role in severe pneumonia children remains to be studied.

Objective: This study focused on the expression and clinical value of miR-125b-5p in severe pneumonia children.

Materials and methods: The study subjects included 96 pneumonia children and 127 severe pneumonia children. These children were aged between 2-10 years. The expression level of serum miR-125b-5p was assessed by qRT-PCR. The receiver operator characteristic (ROC) curve was employed to identify severe pneumonia children from pneumonia individuals. Kaplan-Meier curve was plotted based on follow-up results and multivariate Cox regression analysis was applied to evaluate the contribution of miR-125b-5p to poor prognostic in severe pneumonia children.

Results: MiR-125b-5p was remarkedly reduced in severe pneumonia children compared to pneumonia individuals. The area under the curve (AUC) was 0.9267 and the sensitivity and specificity were 84.25% and 89.58%, respectively. The accumulative survival rate in low miR-125b-5p group showed a remarkable decrease compared to the high miR-125b-5p group (P = 0.033). Increased procalcitonin (PCT, HR: 2.631, 95% CI: 1.029-6.732, P = 0.043) and reduced miR-125b-5p (HR: 0.301, 95% CI: 0.110-0.826, P = 0.020) were found to be related to the poor prognosis in severe pneumonia children.

Conclusion: The reduced miR-125b-5p was an underlying diagnostic indicator of severe pneumonia and was an independent risk factor of poor prognosis in severe pneumonia children.

Objective: To assess the effect of half-dose chemotherapy (HDC) and standard-dose chemotherapy (SDC) on the intestinal microbiota and to investigate whether fecal microbiota transplantation (FMT) can restore the intestinal microecology to enhance the efficacy of chemoimmunotherapy containing an anti-PD- 1 antibody (PD1).

Methods: Lewis lung cancer (LLC) tumor-bearing mice were divided into six groups, including Control, HDC, SDC, SDC + FMT, SDC + PD1, and SDC + PD1 + FMT. After the treatment, analyses were conducted on intestinal microbiota using 16S rRNA sequencing, immune cells through flow cytometry, cytokines and chemokines via polymerase chain reaction (PCR), and programmed death-ligand 1 (PD-L1) expression in tumor tissues by immunohistochemistry.

Results: Alpha and beta diversity of intestinal flora were not significantly different between HDC and SDC groups, nor was there a significant difference in the abundance of the top 10 species at the phylum, class, order, family, genus, or species levels. FMT increased both alpha and beta diversity and led to an increase in the abundance of Ruminococcus_callidus and Alistipes_finegoldii at the species level in mice receiving SDC + FMT. Besides, tumor growth was significantly slowed in SDC + PD1 + FMT compared to SDC + PD1 group, accompanied by an up-regulated Bacteroidetes/Firmicutes ratio, down-regulated abundance of Proteobacteria species (including Pseudolabrys, Comamonas, Alcaligenaceae, Xanthobacteraceae and Comamonadaceae), as well as Faecalicoccus of Firmicutes, the increased number of cDC1 cells, cDC2 cells, CD4⁺ T cells and CD8⁺ T cells in the peripheral blood, and IFN-γ⁺CD8⁺ T cells, IFN-γ, granzyme B, TNF-α, CXCL9 and CXCL10 in intestinal tissues.

Conclusions: There were no significant differences between HDC and SDC in their effects on the intestinal microbiota. FMT exhibited a beneficial impact on gut microbiota and improved the efficacy of chemoimmunotherapy, possibly associated with the increase of immune cells and the modulation of related cytokines and chemokines.

Background: Neutrophils are the first responders to pathogen invasion and are important first-line defenders. The defence mechanism of activated neutrophils includes neutrophil extracellular traps (NETs) formation that immobilize pathogens, stop their spread within the tissues, and ultimately kill them. However, their roles in the context of malaria during pregnancy are still elusive. This study was conducted to investigate markers of neutrophil activation as well as immunological and haematological cellular responses during Plasmodium infection in pregnancy.

Method: A total of 340 pregnant women aged between 19 and 42 years were recruited for this study carried out in South-east, Nigeria. All the subjects were tested for malaria parasite (MP) status. Those infected with human immunodeficiency virus (HIV) and those with any other co-morbidity were excluded from the study. A total of 45 (13.2%) of the 340 pregnant women were positive for malaria. To assess immune, haematologic and NETs markers in the MP positive group, 45 matched malaria-negative pregnant women from the malaria negative group served as controls. Thus, the final study population was grouped into two categories: 45 pregnant women infected with Plasmodium falciparum and 45 pregnant malaria-negative control group. The neutrophil elastase concentration, myeloperoxidase activity, total white blood cell counts, white blood cell differential counts, platelet counts and haematocrit were assessed via standard laboratory methods.

Results: Findings from this study revealed lower levels of myeloperoxidase in the malaria- infected cohort (p = 0.013) than in the malaria negative cohort. The neutrophil elastase levels were also lower in the malaria negative group (p = 0.042). The total white blood cells, platelet and neutrophil counts were lower (p = 0.046, 0.012 and 0.015, respectively) in the malaria infected group when compared to the controls. Conversely, lymphocyte counts were higher in the malaria-infected group (p = 0.003). No cases with high parasitaemia were encountered among the pregnant women infected with Plasmodium falciparum.

Conclusion: Malaria infection led to alterations in immune and haematological parameters in this group, with mild and moderate malaria parasitaemia in the study cohort. Although there were some significant differences, the assessed values remained mostly within the normal range. Further studies in a larger cohort assessing pregnant women infected with placental malaria and those with fatal outcomes are important to further investigate the role of NETs in malaria infection.

Background: Physicians may encounter situations where they need to co-administer omalizumab with non-IgE-targeting monoclonal antibodies. In this study, we share our experience with these dual biologic treatments.

Objective: To evaluate the efficacy and safety of dual biological therapy using omalizumab and non-IgE-targeting monoclonal antibodies at a single center.

Methods: We retrospectively reviewed the medical records of adults treated with a dual biological therapy regimen consisting of omalizumab and another biologic between 2020 and 2022.

Results: Our review identified nine patients (age range: 51-75 years, 7 women and 2 men) who were treated with omalizumab for high Th2 disorders, including chronic spontaneous urticaria (n = 7) and asthma (n = 2). Seven patients received a second biologic for co-existing non-Th2 disorders, while two received an additional biologic to better control their Th2-mediated disorders. The patients were treated with the following biologics: anti-IL-5 agents (mepolizumab [n = 1] and benralizumab [n = 1]), the IL-4/13 inhibitor dupilumab (n = 1), the anti-IL-17 biologic secukinumab (n = 1), the IL-1 inhibitor anakinra (n = 1), the anti-calcitonin gene-related peptide agent fremanezumab (n = 1), and anti-TNF-α agents (etanercept [n = 1], golimumab [n = 1], and adalimumab [n = 1]). Dual biotherapy was administered for 3-34 months with observed clinical improvement. No adverse events or infections were reported.

Conclusions: Dual biological treatment with omalizumab and another biologic appears to be safe, with no need to discontinue non-IgE-targeting agents during omalizumab therapy.

Background: Seronegative Hashimoto's thyroiditis is often underdiagnosed due to the lack of antibody markers. Combining ultrasound radiomics with machine learning offers potential for early detection in patients with normal thyroid function.

Methods: Data from 164 patients with single thyroid lesions and normal thyroid function, treated surgically between 2016 and 2024, were retrospectively collected from four hospitals. Radiomics features were extracted from ultrasound images of non-tumorous hypoechoic areas. Pathological lymphocytic infiltration and hypoechoic ratios were evaluated by senior pathologists and ultrasound physicians. A machine learning model, CCH-NET, was developed using a random forest classifier after feature selection with Least Absolute Shrinkage and Selection Operator (LASSO) regression. The model was trained and tested with an 80:20 split and compared to senior ultrasound physicians.

Results: The CCH-NET model achieved a sensitivity of 0.762, specificity of 0.714, and an area under the curve (AUC) of 0.8248, outperforming senior ultrasound physicians (AUC = 0.681). It maintained consistent accuracy across test sets, with F1 scores of 0.778 and 0.720 in Test_1 and Test_2, respectively, and exhibited superior predictive rates.

Conclusion: The CCH-NET model enhances accuracy in detecting early Seronegative Hashimoto's thyroiditis over senior ultrasound physicians.

Ethics: No. [2023] H013 TRIAL REGISTRATION: Chinese Clinical Trial Registry;CTR2400092179; 12 November 2024.