Exploring the Causal Role of Immune Cells in Cerebral Aneurysm Through Single-Cell Transcriptomics and Mendelian Randomization Analysis.

Cerebral aneurysm (CA) represent a significant clinical challenge, characterized by pathological dilation of cerebral arteries. Recent evidence underscores the crucial involvement of immune cells in CA pathogenesis. This study aims to explore the complex interplay between immune cells and CA formation. We analyzed single-cell RNA sequencing data from the GSE193533 dataset, focusing on unruptured CA and their controls. Comprehensive cell-type identification and pseudotime trajectory analyses were conducted to delineate the dynamic shifts in immune cell populations. Additionally, a two-sample Mendelian Randomization (MR) approach was employed to investigate the causal influence of various immunophenotypes on CA susceptibility and the reciprocal effect of CA formation on immune phenotypes. Single-cell transcriptomic analysis revealed a progressive loss of vascular smooth muscle cells (VSMCs) and an increase in monocytes/macrophages (Mo/MΦ) and other immune cells, signifying a shift from a structural to an inflammatory milieu in CA evolution. MR analysis identified some vital immunophenotypes, such as CD64 on CD14+ CD16+ monocytes (OR: 1.236, 95% CI: 1.064 to 1.435, p=0.006), as potential risk factors for CA development, while others, like CD28- CD8br %CD8br (OR: 0.883, 95% CI: 0.789 to 0.988, p=0.030), appeared protective. Reverse MR analysis demonstrated that CA formation could modulate specific immunophenotypic expressions, highlighting a complex bidirectional interaction between CA pathology and immune response. This study underscores the pivotal role of immune cells in this process through the integration of single-cell transcriptomics with MR analysis, offering a comprehensive perspective on CA pathogenesis, potentially guiding future therapeutic strategies targeting specific immune pathways.

Early life adversity is associated with differential gene expression in immune cells: A cluster-based analysis across an acute psychosocial stressor.

Elucidating mechanisms by which early-life adversity (ELA) contributes to increased disease risk is important for mitigating adverse health outcomes. Prior work has found differences in immune cell gene expression related to inflammation and mitochondrial activity. Using a within-person between-group experimental design, we investigated differences in gene expression clusters across acute psychosocial stress and no-stress conditions. Participants were young adults (N = 29, aged 18 - 25 years, 62 % female, 47 % with a history of ELA). Gene expression was assessed in peripheral blood mononuclear cells collected at 8 blood draws spanning two 5-hour sessions (stress vs. no-stress) separated by a week, 4 across each session (number of observations = 221). We applied two unsupervised gene clustering methods - latent profile analysis (LPA) and weighted gene co-expression analysis (WGCNA) - to cluster genes with similar expression patterns across participants. LPA identified 11 clusters, 7 of which were significantly associated with ELA-status. WGCNA identified 5 clusters, 3 of which were significantly associated with ELA-status. LPA- and WGCNA-identified clusters were correlated, and all clusters were highly preserved across sessions and time. There was no significant effect of acute stress on cluster gene expression, but there was a significant effect of time, and significant differences by ELA-status. ELA-associated clusters related to RNA splicing/processing, inflammation, leukocyte differentiation and division, and mitochondrial activity were differentially expressed across time: ELA-exposed individuals showed decreased expression of these clusters at 90-minutes while controls showed increased expression. Our findings replicate previous work in this area and highlight additional mechanisms by which ELA may contribute to disease risk.

Identification of key mRNAs and signaling pathways in obsessive compulsive disorder based on weighted gene co-expression network analysis and cytoHubba plugin.

PURPOSE: Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder. Genetic and broad environmental factors are common risk factors for OCD. The purpose of this study is to explore the molecular mechanism of OCD and to find new molecular targets for the diagnosis and management of OCD. METHODS: All data were downloaded from public dataset. Key modules and candidate key mRNAs were identified based on weighted gene co-expression network analysis (WGCNA). The "limma" R package was used for differential expression analysis of mRNAs. Subsequently, functional enrichment analysis of differentially expressed mRNAs (DEmRNAs) was also carried out. In addition, a diagnostic model was constructed. Finally, the infiltration level of immune cells in OCD and its correlation with multicentric key DEmRNAs were analyzed. RESULTS: Green and red modules were selected as the hub modules. A total of 447 mRNAs were considered candidate key mRNAs according to GS > 0.2 and MM > 0.3. A total of 26 DEmRNAs in the same direction were identified in the GSE60190 and GSE78104 datasets. A total of 26 DEmRNAs were intersected with candidate key mRNAs in WGCNA to obtain 10 intersection DEmRNAs (HSPB1, ITPK1, CBX7, PPP1R10, TAOK1, PISD, MKNK2, RWDD1, PPA1, and RELN). However, only four DEmRNAs (HSPB1, TAOK1, MKNK2, and PPA1) predicted related drugs. Subsequently, receiver operating characteristic analysis shows that the diagnostic model has high diagnostic value. Moreover, six multicentric key DEmRNAs (SNRPF, SNRNP70, PRPF8, NOP56, EPRS, and CCT2) were screened by UpSet package. Finally, six multicentric key DEmRNAs were found to be associated with immune cells. CONCLUSION: The key molecules obtained in this study lay a foundation for further research on the molecular mechanism of OCD.

Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis.

Background: Little is known about the prevalence of cellular senescence among immune cells (i.e., immune cells expressing senescence markers, iSCs) nor is there a gold-standard to efficiently measure iSCs. Major depressive disorder (MDD) in older adults has been associated with many hallmarks of senescence in whole blood, leukocytes, and plasma, supporting a strong connection between iSCs and MDD. Here, we investigated the prevalence and phenotype of iSCs in older adults with MDD. Using a single-cell phenotypic approach, circulating immune cells were examined for iSC biomarkers and their relationship to depression and inflammation. Results: PBMCs from older adults with MDD (aged 69.75 ± 5.23 years) and healthy controls (aged 71.25 ± 8.8 years) were examined for immune subset distribution and senescence biomarkers (i.e., lack of proliferation, senescence-associated heterochromatin foci (SAHF), and DNA damage). Dual-expression of SAHF and DNA damage was categorized by low, intermediate, and high expression. A significant increase in the number of high expressing total PBMCs (p = 0.01), monocytes (p = 0.008), a trending increase in the number of high expressing CD4 T cells (p = 0.06) was observed overall in those with MDD. There was also a significantly lower proportion of intermediate expressing cells in monocytes and CD4 T cells in MDD (p = 0.01 and p = 0.05, respectively). Correlation analysis revealed associations between iSCs and mRNA expression of factors related to SASP and immune cell function. Conclusion: MDD is associated with increased senescent cell biomarkers in immune cell populations delineated by distinct levels of SAHF and DNA damage. Inflammatory markers might serve as potent indicators of iSC burden in MDD.

Advanced in immunological monitoring of HIV infection: profile of immune cells and cytokines in people living with HIV-1 in Benin.

BACKGROUND: Immune cells and cytokines have been linked to viremia dynamic and immune status during HIV infection. They may serve as useful biomarkers in the monitoring of people living with HIV-1 (PLHIV-1). The present work was aimed to assess whether cytokines and immune cell profiles may help in the therapeutic follow-up of PLHIV-1. METHODS: Forty PLHIV-1 in treatment success (PLHIV-1s) and fifty PLHIV-1 in treatment failure (PLHIV-1f) followed at the University Hospital of Abomey-Calavi/Sô-Ava in Benin were enrolled. Twenty healthy persons were also recruited as control group. Circulating cytokines and immune cells were quantified respectively by ELISA and flow cytometry. RESULTS: PLHIV-1 exhibited low proportions of CD4 + T cells, NK, NKT, granulocytes, classical and non-classical monocytes, and high proportions of CD8 + T cells, particularly in the PLHIV-1f group, compared to control subjects. Eosinophils, neutrophils and B cell frequencies did not change between the study groups. Circulating IFN-γ decreased whereas IL-4 significantly increased in PLHIV-1s compared to PLHIV-1f and control subjects even though the HIV infection in PLHIV-1s downregulated the high Th1 phenotype observed in control subjects. However, Th1/Th2 ratio remained biased to a Th1 phenotype in PLHIV-1f, suggesting that high viral load may have maintained a potential pro-inflammatory status in these patients. Data on inflammatory cytokines showed that IL-6 and TNF-α concentrations were significantly higher in PLHIV-1s and PLHIV-1f groups than in control subjects. Significant high levels of IL-5 and IL-7 were observed in PLHIV-1f compared to controls whereas PLHIV-1s presented only a high level of IL-5. No change was observed in IL-13 levels between the study groups. CONCLUSION: Our study shows that, in addition to CD4/CD8 T cell ratio, NK and NKT cells along with IL-6, TNF-α, IL-5 and IL-7 cytokines could serve as valuable immunological biomarkers in the therapeutic monitoring of PLHIV-1 although a larger number of patients would be necessary to confirm these results.

Verification of the expression trend and interaction prediction of innate immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis.

OBJECTIVES: This study aimed to explore the expression trends of innate immune cells and immune-checkpoint molecules validated by data calculation in the process of oral mucosal carcinogenesis, as well as to explore methods of suppressing oral mucosal carcinogenesis based on immunotherapy by predicting their interactions. Me-thods 1) The cancer genome atlas (TCGA) database comprehensively scores immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis and screens out intrinsic immune cells and immune-checkpoint molecules that interfere with tumor immune escape. 2) Clinical patient blood routine data were collected for the statistical analysis of peripheral blood immune cells during the progression of oral mucosal carcinogenesis. Immune cells in peripheral blood that may affect the progression of oral mucosal carcinogenesis were screened. 3) Immunohistochemical staining was performed on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation in various stages of oral mucosal carcinogenesis. 4) Special staining was used to identify innate immune cells in various stages of oral mucosal carcinogenesis based on data-calculation verification. 5) Survival analysis was conducted on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation during the process of oral mucosal carcinogenesis. The association of intrinsic immune cells and immune-checkpoint molecules with the prognosis of oral squamous cell carcinoma was verified. RESULTS: The expression of monocytes and neutrophils increased during the process of oral mucosal carcinogenesis. The expression of eosinophils showed a single peak trend of up and down. The expression of mast cells decreased. In the process of oral mucosal carcinogenesis, the expression of the immune-checkpoint molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death-ligand (PD-L1) increased. The expression trends of monocytes, neutrophils, and eosinophils were positively correlated with those of CTLA4 and PD-L1 immune-checkpoint molecules. The expression trend of mast cells was negatively correlated with the expression of CTLA4 and PD-L1. Monocytes, neutrophils, and eosinophils may promote tumor immune escape mediated by CTLA4 and/or PD-L1, thereby accelerating the progression of oral mucosal carcinogenesis. Mast cells may inhibit tumor immune escape mediated by CTLA4 and/or PD-L1, delaying the progression of oral mucosal carcinogenesis. CONCLUSIONS: Therefore, interference with specific immune cells in innate immunity can regulate the expression of CTLA4 and/or PD-L1 to a certain extent, inhibit tumor immune escape, and delay the progression of oral mucosal carcinogenesis.

A 15-Inflammation-Related Gene Signature Predicts the Prognosis of Patients With Pancreatic Ductal Adenocarcinoma.

Chronic inflammation promotes the development of pancreatic ductal adenocarcinoma (PDAC) and PDAC-related inflammatory tumor microenvironment facilitates tumor growth and metastasis. Thus, we aimed to study the association between inflammatory response and prognosis in patients with PDAC. We conducted the whole transcriptomic sequencing using tissue samples collected from patients diagnosed with PDAC (n = 106) recruited from Shandong Cancer Hospital. We first constructed a prognostic signature using 15 inflammation-related genes in The Cancer Genome Atlas (TCGA) cohort (n = 177) and further validated it in an independent International Cancer Genome Consortium (ICGC) cohort (n = 90) and our in-house cohort. PDAC patients with a higher risk score had poorer overall survival (OS) (P < 0.001; HR, 3.02; 95% CI, 1.94-4.70). The association between the prognostic signature and OS remained significant in the multivariable Cox regression adjusting for age, sex, alcohol exposure, diabetes, and stage (P < 0.001; HR, 2.91; 95% CI, 1.73-4.89). This gene signature also robustly predicted prognosis in the ICGC cohort (P = 0.01; HR, 1.94; 95% CI, 1.14-3.30) and our cohort (P < 0.001; HR, 2.40; 95% CI, 1.45-3.97). Immune subtype C3 (inflammatory) was enriched and CD8+ T cells were higher in patients with a lower risk score (P < 0.05). Furthermore, PDAC patients with higher risk scores were more sensitive to chemotherapy, immunotherapy, and PARP inhibitors (P < 0.05). In sum, we identified a novel gene signature that was associated with inflammatory response for risk stratification, prognosis prediction, and therapy guidance in PDAC patients. Future studies are warranted to validate the clinical utility of the signature.

Exposure to per- and polyfluoroalkyl substances in lung cancer patients and their associations with clinical health indicators.

Per- and polyfluoroalkyl substances (PFASs) have potential carcinogenicity, immunotoxicity, and hepatotoxicity. Research has been conducted on PFAS exposure in people to discuss their potential health effects, excluding lung cancer. In this study, we recruited participants (n = 282) with lung cancer from Heilongjiang Province, northeast China. The PFAS concentrations were measured in their serum to fill the data gap of exposure, and relationships were explored in levels between PFASs and clinical indicators of tumor, immune and liver function. Ten PFASs were found in over 80 % of samples and their total concentrations were 5.27-152 ng/mL, with the highest level for perfluorooctanesulfonate (median: 12.4 ng/mL). Long-chain PFASs were the main congeners and their median concentration (20.5 ng/mL) was nearly three times to that of short-chain PFASs (7.61 ng/mL). Significantly higher concentrations of perfluorobutanoic acid, perfluorononanoic acid and perfluorohexanesulfonate were found in males than in females (p < 0.05). Serum levels of neuro-specific enolase were positively associated with perfluoropentanoic acid in all participants and were negatively associated with perfluorononanesulfonate in females (p < 0.05, multiple linear regression models). Exposure to PFAS mixture was significantly positively associated with the lymphocytic absolute value (difference: 0.224, 95% CI: 0.018, 0.470; p < 0.05, quantile g-computation models) and serum total bilirubin (difference: 2.177, 95% CI: 0.0335, 4.33; p < 0.05). Moreover, PFAS exposure can affect γ-glutamyl transpeptidase through several immune markers (p < 0.05, mediating test). Our results suggest that exposure to certain PFASs could interfere with clinical indicators in lung cancer patients. To our knowledge, this is the first study to detect serum PFAS occurrence and check their associations with clinical indicators in lung cancer patients.

Integrated bioinformatics analysis reveals upregulated extracellular matrix hub genes in pancreatic cancer: Implications for diagnosis, prognosis, immune infiltration, and therapeutic strategies.

BACKGROUND: Pancreatic cancer (PC) stands out as one of the most formidable malignancies and exhibits an exceptionally unfavorable clinical prognosis due to the absence of well-defined diagnostic indicators and its tendency to develop resistance to therapeutic interventions. The primary objective of this present study was to identify extracellular matrix (ECM)-related hub genes (HGs) and their corresponding molecular signatures, with the intent of potentially utilizing them as biomarkers for diagnostic, prognostic, and therapeutic applications. METHODS: Three microarray datasets were sourced from the NCBI database to acquire upregulated differentially expressed genes (DEGs), while MatrisomeDB was employed for filtering ECM-related genes. Subsequently, a protein-protein interaction (PPI) network was established using the STRING database. The created network was visually inspected through Cytoscape, and HGs were identified using the CytoHubba plugin tool. Furthermore, enrichment analysis, expression pattern analysis, clinicopathological correlation, survival analysis, immune cell infiltration analysis, and examination of chemical compounds were carried out using Enrichr, GEPIA2, ULCAN, Kaplan Meier plotter, TIMER2.0, and CTD web platforms, respectively. The diagnostic and prognostic significance of HGs was evaluated through the ROC curve analysis. RESULTS: Ten genes associated with ECM functions were identified as HGs among 131 DEGs obtained from microarray datasets. Notably, the expression of these HGs exhibited significantly (p < 0.05) higher in PC, demonstrating a clear association with tumor advancement. Remarkably, higher expression levels of these HGs were inversely correlated with the likelihood of patient survival. Moreover, ROC curve analysis revealed that identified HGs are promising biomarkers for both diagnostic (AUC > 0.75) and prognostic (AUC > 0.64) purposes. Furthermore, we observed a positive correlation between immune cell infiltration and the expression of most HGs. Lastly, our study identified nine compounds with significant interaction profiles that could potentially act as effective chemical agents targeting the identified HGs. CONCLUSION: Taken together, our findings suggest that COL1A1, KRT19, MMP1, COL11A1, SDC1, ITGA2, COL1A2, POSTN, FN1, and COL5A1 hold promise as innovative biomarkers for both the diagnosis and prognosis of PC, and they present as prospective targets for therapeutic interventions aimed at impeding the progression PC.

Causal relationship between the immune cells and ankylosing spondylitis: univariable, bidirectional, and multivariable Mendelian randomization.

Background: Ankylosing spondylitis (AS) is an autoimmune disease that affects millions of individuals. Immune cells have been recognized as having a crucial role in the pathogenesis of AS. However, their relationship has not been fully explored. Methods: We chose to employ Mendelian randomization (MR) to investigate the potential correlation between immune cells and AS. We sourced the data on immune cells from the latest genome-wide association studies (GWASs). We obtained data on AS from the FinnGen consortium. Our comprehensive univariable MR analysis covered 731 immune cells to explore its potential causal relationship with AS. The primary analysis method was inverse-variance weighted (IVW). Additionally, we used Cochran's Q test and the MR-Egger intercept test to assess the presence of pleiotropy and heterogeneity. We examined whether our results could be influenced by individual single-nucleotide polymorphisms (SNPs) using the leave-one-out test. We conducted a bidirectional MR to investigate the reverse relationship. We also applied multivariable MR to decrease the potential influence between the immune cells. Results: Overall, our univariable MR analysis revealed eight immune cells associated with AS. Among these, four immune cells contributed to an increased risk of AS, while four immune cells were identified as protective factors for AS. However, the Bonferroni test confirmed only one risk factor and one protective factor with a significance level of p < 6.84E-05. CD8 on effector memory CD8+ T cell could increase the risk of AS (p: 1.2302E-05, OR: 2.9871, 95%CI: 1.8289-4.8786). HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 1.2301E-06, OR: 0.5446, 95%CI: 0.4260-0.6962). We also identified a bidirectional relationship between CD4 on CD39+ activated CD4 regulatory T cells and AS utilizing the bidirectional MR. To address potential confounding among immune cells, we employed multivariable MR analysis, which revealed that only one immune cell had an independent effect on AS. HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 2.113E-06, OR: 0.0.5423, 95%CI: 0.4210-0.6983). Our findings were consistently stable and reliable. Conclusions: Our findings indicated a potential link between immune cells and AS, which could provide a new idea for future research. Nevertheless, the specific underlying mechanisms require further exploration.

BCL9 is a Risk Factor of Neck Lymph Nodes Metastasis and Correlated with Immune Cell Infiltration in Papillary Thyroid Carcinoma.

Purpose: B-cell lymphoma 9 (BCL9), a key transcription co-activator of the Wnt pathway, contributed to tumor progression and metastasis in various tumors, whereas, the role of BCL9 in papillary thyroid cancer (PTC) has not been investigated. Methods: We acquired PTC gene expression data from The Cancer Genome Atlas (TCGA) database. Fifty-nine PTC tissues were applied to validate the clinical significance of BCL9. Cell experiments were applied to investigate the role of BCL9. Bioinformatics analysis was employed to investigate the biological functions of BCL9. Results: We found that BCL9 was higher expressed (P < 0.05) and an independent risk factor for lymph node metastasis (OR = 3.770, P = 0.025), as well as associated with poorer progression-free survival (PFS) (P = 0.049) in PTC. BCL9 knockdown inhibited proliferation and invasion of PTC cells. BCL9 was positively associated with the key genes of Wnt/ß-catenin and MAPK pathway by co-expression analysis. GO, KEGG and GSEA analysis showed BCL9 might participated in PPAR, cAMP, and focal adhesion pathway. CIBERSORT analysis found BCL9 was negatively associated with CD8+ T cells and NK cell infiltration and positively with PD-L1 expression. Conclusion: Therefore, BCL9 was associated with lymph node metastasis and shorter PFS of PTC, due to promotion of PTC cell proliferation and invasion, activation of Wnt/ß-catenin and MAPK pathway, inhibition of CD8+ T and NK cell infiltration, and promotion of PD-L1 expression.

Antiviral immunity of severe fever with thrombocytopenia syndrome: current understanding and implications for clinical treatment.

Dabie Banda virus (DBV), a tick-borne pathogen, was first identified in China in 2009 and causes profound symptoms including fever, leukopenia, thrombocytopenia and multi-organ dysfunction, which is known as severe fever with thrombocytopenia syndrome (SFTS). In the last decade, global incidence and mortality of SFTS increased significantly, especially in East Asia. Though previous studies provide understandings of clinical and immunological characteristics of SFTS development, comprehensive insight of antiviral immunity response is still lacking. Here, we intensively discuss the antiviral immune response after DBV infection by integrating previous ex- and in-vivo studies, including innate and adaptive immune responses, anti-viral immune responses and long-term immune characters. A comprehensive overview of potential immune targets for clinical trials is provided as well. However, development of novel strategies for improving the prognosis of the disease remains on challenge. The current review may shed light on the establishment of immunological interventions for the critical disease SFTS.

The role of CCL2/CCR2 axis in cancer and inflammation: The next frontier in nanomedicine.

The communication between cells and their microenvironment represents an intrinsic and essential attribute that takes place in several biological processes, including tissue homeostasis and tissue repair. Among these interactions, inflammation is certainly a central biological response that occurs through cytokines and the crosstalk with their respective receptors. In particular, the interaction between CCL2 and its main receptor, CCR2, plays a pivotal role in both harmful and protective inflammatory states, including cancer-mediated inflammation. The activation of the CCL2/CCR2 axis was shown to dictate the migration of macrophages with immune-suppressive phenotype and to aggravate the progression of different cancer types. In addition, this interaction mediates metastasis formation, further limiting the potential therapeutic outcome of anti-cancer drugs. Attempts to inhibit pharmacologically the CCL2/CCR2 axis have yet to show its anti-cancer efficacy as a single agent, but it sheds light on its role as a powerful tool to selectively alleviate pro-tumorigenic and anti-repair inflammation. In this review, we will elucidate the role of CCL2/CCR2 axis in promoting cancer inflammation by activating the host pro-tumorigenic phenotype. Moreover, we will provide some insight into the potential therapeutic benefit of targeting the CCL2/CCR2 axis for cancer and inflammation using novel delivery systems, aiming to sensitize non-responders to currently approved immunotherapies and offer new combinatory approaches.

Fluid-Dynamic Culture of Tumour and Immune Cells for More Predictive Infiltration Studies and Immunotherapy Drug Screening.

Immunotherapies represent one of the current most promising challenges in cancer treatment. They are based on the boost of natural immune responses, aimed at cancer eradication. However, the success of immunotherapeutic approaches strictly depends on the interaction between immune cells and cancer cells. Preclinical drug tests currently available are poor in fully predicting the actual safety and efficacy of immunotherapeutic treatments under development. Indeed, conventional 2D cell culture underrepresents the complexity of the tumour microenvironment, while in vivo animal models lack in mimicking the human immune cell responses. In this context, predictability, reliability, and complete immune compatibility still represent challenges to overcome. For this aim, novel 3D, fully humanized in vitro cancer tissue models have been recently optimized by adopting emerging technologies, such as organ-on-chips (OOC) and 3D cancer cell-laden hydrogels. In particular, a novel multi-in vitro organ (MIVO) OOC platform has been recently adopted to culture 3D clinically relevant size cancer tissues under proper physiological culture conditions to investigate anti-cancer treatments and immune-tumour cell crosstalk.The proposed immune-tumour OOC-based model offers a potential tool for accurately modelling human immune-related diseases and effectively assessing immunotherapy efficacy, finally offering promising experimental approaches for personalized medicine.

Formation of Mycobacterium abscessus colonies in cellular culture in an in vitro infection model.

Mycobacterium abscessus is one of the most important nontuberculous mycobacteria that cause lung diseases. In vitro infection models developed to analyze the immune response are frequently based on the addition of mycobacteria to mononuclear cells or neutrophils from peripheral blood. An important requirement of these assays is that most cells phagocytose mycobacteria, only accomplished by using large multiplicities of infection (1 or more bacteria per cell) which may not adequately reflect the inhalation of a few mycobacteria by the host. We propose modifications that try to mimic some of the conditions in which immune cells deal with mycobacteria. For the preparation of the inoculum mycobacteria are grown in solid media followed by preparation to a single cell suspension. Multiplicities of infection (number of bacteria per cell) are below 0.01. Serum-free cellular media is used to allow the growth of M. abscessus. After several days of incubation Bacterial Colonies in Cellular Culture (BCCC) develop, which are enumerated directly under an inverted microscope. These colonies may represent biofilm formation during chronic infections. •Low multiplicity of infection (below 0.01 bacteria per cell) reflects more realistically conditions encountered by immune cells in the lungs.•The surface of mycobacteria prepared for infection assays that are grown in solid media are less affected than that of mycobacteria grown in liquid media with detergents.•Colony formation in the infected cells may reflect the aggregation and biofilm formation in the lungs during chronic infection.

Causal relationship between immune cells and prostate cancer: a Mendelian randomization study.

Introduction: Despite the abundance of research indicating the participation of immune cells in prostate cancer development, establishing a definitive cause-and-effect relationship has proven to be a difficult undertaking. Methods: This study employs Mendelian randomization (MR), leveraging genetic variables related to immune cells from publicly available genome-wide association studies (GWAS), to investigate this association. The primary analytical method used in this study is inverse variance weighting (IVW) analysis. Comprehensive sensitivity analyses were conducted to assess the heterogeneity and horizontal pleiotropy of the results. Results: The study identifies four immune cell traits as causally contributing to prostate cancer risk, including CD127- CD8+ T cell %CD8+ T cell (OR = 1.0042, 95%CI:1.0011-1.0073, p = 0.0077), CD45RA on CD39+ resting CD4 regulatory T cell (OR = 1.0029, 95%CI:1.0008-1.0050, p = 0.0065), CD62L- Dendritic Cell Absolute Count (OR = 1.0016; 95%CI:1.0005-1.0026; p = 0.0039), CX3CR1 on CD14+ CD16- monocyte (OR = 1.0024, 95%CI:1.0007-1.0040, p = 0.0060). Additionally, two immune cell traits are identified as causally protective factors: CD4 on monocyte (OR = 0.9975, 95%CI:0.9958-0.9992, p = 0.0047), FSC-A on plasmacytoid Dendritic Cell (OR = 0.9983, 95%CI:0.9970-0.9995, p = 0.0070). Sensitivity analyses indicated no horizontal pleiotropy. Discussion: Our MR study provide evidence for a causal relationship between immune cells and prostate cancer, holding implications for clinical diagnosis and treatment.

Harnessing Immune Cell Metabolism to Modulate Alloresponse in Transplantation.

Immune cell metabolism plays a pivotal role in shaping and modulating immune responses. The metabolic state of immune cells influences their development, activation, differentiation, and overall function, impacting both innate and adaptive immunity. While glycolysis is crucial for activation and effector function of CD8 T cells, regulatory T cells mainly use oxidative phosphorylation and fatty acid oxidation, highlighting how different metabolic programs shape immune cells. Modification of cell metabolism may provide new therapeutic approaches to prevent rejection and avoid immunosuppressive toxicities. In particular, the distinct metabolic patterns of effector and suppressive cell subsets offer promising opportunities to target metabolic pathways that influence immune responses and graft outcomes. Herein, we review the main metabolic pathways used by immune cells, the techniques available to assay immune metabolism, and evidence supporting the possibility of shifting the immune response towards a tolerogenic profile by modifying energetic metabolism.

Causal role of immune cells in psoriasis: a Mendelian randomization analysis.

Background: A growing body of evidence has shown that immune cells are linked to psoriasis. It is, however, still unclear if these associations reflect a relationship of cause and effect. Objective: We employed a two-sample Mendelian randomization (MR)-based study to elucidate the probable causative connection between immune cells and psoriasis. Methods: Summary information for psoriasis (Ncase = 5,427, Ncontrol = 479,171) was obtained from the European Bioinformatics Institute. Summarized statistical information on 731 immune cell features, including morphological parameters (MP; n = 32), relative cell number (n = 192), median fluorescence intensity (MFI) of surface antigens (n = 389), and absolute cell number (n = 118), was obtained from the genome-wide association studies (GWAS) catalog. The research consisted of forward MR analysis, in which immune cell traits were used as the exposure factor, and psoriasis was the outcome, as well as reverse MR analysis, in which psoriasis was used as the exposure factor, and immune cell traits were the outcome. We ran numerous sensitivity analyses to ascertain the study results for robustness, heterogeneity, and potential multiple-biological effects. Result: This research determined a probable causative connection between immune cells and psoriasis. In particular, we identified 36 distinct types of immune cells that are potentially causally linked to psoriasis. Conclusion: Our findings indicate strong causal correlations between 36 immunological phenotypes and psoriasis, thus, directing future clinical trials.

Correlation of caecal microbiome endotoxins genes and intestinal immune cells in Eimeria tenella infection based on bioinformatics.

Introduction: The infection with Eimeria tenella (ET) can elicit expression of various intestinal immune cells, incite inflammation, disrupt intestinal homeostasis, and facilitate co-infection with diverse bacteria. However, the reciprocal interaction between intestinal immune cells and intestinal flora in the progression of ET-infection remains unclear. Objective: The aim of this study was to investigate the correlation between cecal microbial endotoxin (CME)-related genes and intestinal immunity in ET-infection, with subsequent identification of hub potential biomarker and immunotherapy target. Methods: Differential expression genes (DEGs) within ET-infection and hub genes related to CME were identified through GSE39602 dataset based on bioinformatic methods and Protein-protein interaction (PPI) network analysis. Moreover, immune infiltration was analyzed by CIBERSORT method. Subsequently, comprehensive functional enrichment analyses employing Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis along with Gene Ontology (GO), gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were performed. Results: A total of 1089 DEGs and 25 hub genes were identified and CXCR4 was ultimately identified as a essential CME related potential biomarker and immunotherapy target in the ET-infection. Furthermore, activated natural killer cells, M0 macrophages, M2 macrophages, and T regulatory cells were identified as expressed intestinal immune cells. The functional enrichment analysis revealed that both DEGs and hub genes were significantly enriched in immune-related signaling pathways. Conclusion: CXCR4 was identified as a pivotal CME-related potential biomarker and immunotherapy target for expression of intestinal immune cells during ET-infection. These findings have significant implications in elucidating the intricate interplay among ET-infection, CME, and intestinal immunity.

Causal Role of Immune Cells in Chronic Obstructive Pulmonary Disease: A Two-Sample Mendelian Randomization Study.

Accumulating evidence has highlighted the importance of immune cells in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the understanding of the causal association between immunity and COPD remains incomplete due to the existence of confounding variables. In this study, we employed a two-sample Mendelian randomization (MR) analysis, utilizing the genome-wide association study database, to investigate the causal association between 731 immune-cell signatures and the susceptibility to COPD from a host genetics perspective. To validate the consistency of our findings, we utilized MR analysis results of lung function data to assess directional concordance. Furthermore, we employed MR-Egger intercept tests, Cochrane's Q test, MR-PRESSO global test, and "leave-one-out" sensitivity analyses to evaluate the presence of horizontal pleiotropy, heterogeneity, and stability, respectively. Inverse variance weighting results showed that seven immune phenotypes were associated with the risk of COPD. Analyses of heterogeneity and pleiotropy analysis confirmed the reliability of MR results. These results highlight the interactions between the immune system and the lungs. Further investigations into their mechanisms are necessary and will contribute to inform targeted prevention strategies for COPD.