Immune Cell Counts Research Articles

The Order of Concurrent Training Affects Acute Immunological Stress Responses and Measures of Muscular Fitness in Female Youth Judo Athletes.

This study aimed to examine the acute effects of concurrent muscle strength and sport-specific endurance exercise order on immunological stress responses, metabolic response, muscular-fitness, and rating-of-perceived-exertion (RPE) in highly trained youth female judo athletes. Thirteen female participants randomly performed two concurrent training (CT) sessions; strength-endurance and endurance-strength. Immune response, metabolic response, muscular fitness (i.e., countermovement jump-derived force and power [CMJ-force and CMJ-power]), and RPE were measured at different time points (i.e., PRE, MID, POST, POST6h, and POST22h). There were significant time×order interactions for lymphocytes (p=0.006, ES=1.31), granulocyte-lymphocyte ratio (p=0.002, ES=1.56), and systemic inflammation index (p=0.029, ES=1.11), blood glucose and lactate (p<0.001, ES=2.09 and p=0.0018, ES=1.51, respectively), CMJ-force (p=0.033, ES=1.26), and CMJ-power (p=0.007, ES=1.40) as well as RPE (p<0.001, ES=2.05). CT-induced acute (i.e., POST) but not delayed (i.e., POST6h and POST22h) order-dependent immune cell count alterations in highly trained youth female judo athletes. All markers of the immune system went back to baseline values at POST22h. Metabolic responses were slightly higher following the endurance exercise (irrespective of the applied exercise order). CMJ-measures and RPE fluctuated during both CT sessions but returned to baseline 6h post-exercise.

The association between systemic inflammation markers and the risk of incident dilated cardiomyopathy: a prospective study of 351,148 participants

Background The role of systemic inflammation in the development and progression of cardiovascular diseases has been attractive, but its association with incident dilated cardiomyopathy (DCM) is rarely investigated. This study aimed to systematically investigate the association between various inflammatory markers and DCM incidence. Methods The data were derived from the UK Biobank database. Systemic inflammation markers in this study encompassed peripheral immune cell counts and their ratios and the low-grade inflammation score (INFLA-score). The Cox proportional hazards regression, restricted cubic splines model, and segmented regression were adopted to assess the association between systemic inflammation markers and DCM incidence. Additionally, the subgroup Cox analysis stratified across sex was also performed. Results A total of 351,148 participants were enrolled in this study, and 377 subjects developed DCM during a mean follow-up of 12.21 years. The positive association between C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and CRP-to-lymphocyte ratio (CLR) and DCM incident risk was found (CRP: HR = 1.190, P = 0.001; NLR: HR = 1.315, P = 0.033; CLR: HR = 1.206, P < 0.001), while the lymphocyte-to-monocyte ratio (LMR) was negatively associated with DCM incident risk (HR = 0.756; P = 0.033). Furthermore, the increased risk of DCM incidence was significantly and nonlinearly correlated with the reduction of platelet count (HR = 0.543; P = 0.002). In the subgroup analysis, sex-specific inflammation markers related to DCM development were noticed. Conclusions The study has underlined that multiple inflammation markers were significantly associated with the risk of incident DCM, which would provide evidence for the aetiological study of DCM.

P-2177. The Prevalence of Respiratory Viral Pathogen Detection on Nasopharyngeal Specimens Evaluated by Multiplex Polymerase Chain Reaction Among Asymptomatic Children

Abstract Background While current viral detection methods demonstrate high sensitivity, their clinical relevance remains inexact. We evaluated the prevalence of respiratory viral pathogen detection (RVPD) using multiplex polymerase chain reaction (M-PCR) and its correlation with nasal immune cell quantities and reported respiratory viral symptoms (RVS) in asymptomatic or pauci-symptomatic children. Demographic and Clinical Characteristics of 20 Children at Enrollment in the Pediatric Respiratory Co-infection and Immunologic Response Study (Peds RECON) Legend: ^= Nasopharyngeal specimens were processed using the BioFire® Respiratory 2.1 (RP2.1) Panel * = within 10 days of the participant’s enrollment visit + = Symptoms queried: fever, headache, runny or dripping nose, sore or painful throat, trouble breathing/shortness of breath, chest tightness/pain, dizziness, coughing, nausea, vomiting, diarrhea, clingy, fussy, decreased energy level #= Among 15 participants where blood sample was available; 4 of 7 participants with positive M-PCR and 11 of 13 participants with negative M-PCR NP=Nasopharyngeal; SD= Standard deviation; M- PCR= Multiplex Polymerase Chain Reaction Methods The ongoing Pediatric Respiratory Co-infection and Immunologic Response Study (Peds RECON) measures clinical and immune responses during respiratory viral infections in participants aged 1 month to 17 years, enrolled while healthy, with follow-up visits during illness over two years. Enrollment involves demographic data collection, a 10-day respiratory symptom review, and sample collection (nasopharyngeal (NP) swab and peripheral blood (PB)). NP swabs undergo M-PCR using the BioFire® Respiratory 2.1 panel, and both NP swabs and PB samples undergo immune cell quantification. A prevalence rate was calculated based on M-PCR-positive NP swabs per all collected NP swabs. A t-test compared NP immune cell counts between participants with and without RVPD at enrollment, while logistic regression assessed the association with RVS and RVPD. Participant Findings by Multiplex PCR Positivity in 20 Peds RECON Participants at Enrollment Legend: += positive -= Negative ^= Rhinovirus/Enterovirus and Parainfluenza 3 #=Number NS= not significant, p-value ≥ 0.05 Peds RECON- Pediatric Respiratory Co-infection and Immunologic Response Study NP= Nasopharyngeal (NP) M-PCR= Multiplex Polymerase Chain Reaction, Nasopharyngeal specimens were processed using the BioFire® Respiratory 2.1 (RP2.1) Panel PBMC=Peripheral Blood Mononuclear Cells Results From January to May 2024, 20 children (median age: 11 years) were enrolled (table). Most reported respiratory illness ≥4 weeks prior (n=16). Seven NP swabs tested positive among 20 NP swabs (35% prevalence rate), primarily rhinovirus/enterovirus. At enrollment, 45% reported at least one respiratory symptom in the preceding 10 days. The mean nasal immune cell count was 85,920 (SD: 74,872), with no significant association between RVPD and immune cell counts (t (18) =0.27, p=0.80) or RVS (OR: 0.88; 95% CI: 0.14; 5.58) (figure A; D). Conclusion Thirty-five percent of apparently healthy children in Peds RECON had a RVP detected on M-PCR, highlighting the discrepancy between clinical appearance and RVPD. Nasopharyngeal cell isolation did not correlate with positive M-PCR or reported symptoms, demonstrating M-PCR positivity for certain pathogens is indicative of asymptomatic presence of viral RNA. Further research is required to determine if asymptomatic shedding occurs or if the sensitivity of the assay for certain pathogens requires optimization. Disclosures All Authors: No reported disclosures

Impact of risk factors in craniofacial mucormycosis.

Craniofacial mucormycosis is a highly lethal infectious disease. This study aims to assess and analyze multiple variables, including clinical, socioeconomic, and biochemical markers, to identify and examine risk factors for mortality associated with this mycotic infection. A retrospective analysis was conducted on 38 patients who sought medical attention at the Otolaryngology and Head and Neck Surgery Division of a tertiary-level hospital in Monterrey, Mexico. A broad range of variables was analyzed: clinical features, including the extent of mucormycosis infection; socioeconomic factors such as monthly income, marital status, geographical residence, educational level, and insurance status; as well as biochemical markers, including glucose levels, lactate dehydrogenase (LDH), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and immune cell counts, specifically neutrophils (NEU) and lymphocytes (LYM). Statistical analysis was conducted using SPSS v26. Risk factors for mortality were evaluated using Cox regression. Overall survival (OS) was assessed with the Kaplan-Meier method. The Fisher's exact test and the Chi-square test were used for categorical variables. For median comparisons, the Student's t-test and Mann-Whitney U test were applied; with normality assessed using the Shapiro-Wilk test. A p-value <0.05 was considered statistically significant. Mucormycosis was associated with higher mortality in men (p=0.032). The disease primarily affected the paranasal sinuses (p=0.021) and was associated with increased mortality when involving the orbit (p=0.035). Additionally, compromised lymphocyte counts (LYM) (p=0.034) and lower educational levels (p=0.009) were associated with higher mortality. Individuals residing in rural areas also exhibited an elevated risk of mortality (p =0.023). Prevention strategies should focus on high-risk groups to reduce the mortality rate of craniofacial mucormycosis, particularly targeting men and individuals residing in rural areas. Special emphasis should be placed on those without education or health insurance. Early diagnosis and appropriate management are crucial for improving outcomes.

Fasting plasma methylglyoxal concentrations are associated with higher numbers of circulating intermediate and non-classical monocytes but with lower activation of intermediate monocytes: the Maastricht Study.

Elevated methylglyoxal (MGO) levels and altered immune cell responses are observed in diabetes. MGO is thought to modulate immune cell activation. The current study investigated whether fasting or post-glucose-load plasma MGO concentrations are associated with circulating immune cell counts and activation in a large cohort study. 696 participants of The Maastricht Study (age 60.3 ± 8.4 years, 51.9% women) underwent an oral glucose tolerance test (OGTT). Fasting and post-OGTT plasma MGO concentrations were measured using mass spectrometry. Numbers and activation of circulating immune cells at fasting state were quantified using flow cytometry. Activation scores were calculated by averaging individual marker z-scores for neutrophils (CD11b, CD11c, CD16) and classical, intermediate, and non-classical monocytes (CD11b, CD11c, CX3XR1, HLA-DR). Associations were analysed using multiple linear regression adjusted for potential confounders. Stratified analyses were performed for glucose metabolism status for associations between plasma MGO levels and immune cell counts. Higher fasting plasma MGO concentrations were significantly associated with higher numbers of intermediate (β = 0.09 [95%CI 0.02; 0.17]) and non-classical monocytes (0.08 [0.002; 0.15]), but with lower activation scores for the intermediate monocytes (-0.14 [-0.22; -0.06]). Stratified analyses showed that positive associations between fasting plasma MGO levels and numbers of intermediate and non-classical monocytes appear only in participants with type 2 diabetes. Post-OGTT plasma MGO concentrations were not consistently associated with immune cells counts or activation. Higher fasting plasma MGO concentrations are associated with higher intermediate and non-classical monocyte counts but with lower activation of intermediate monocytes.

Identifying Neuro-inflammatory Biomarkers of Generalized Anxiety Disorder from Lymphocyte Subsets based on machine learning approaches.

Activation of the inflammatory response system is involved in the pathogenesis of generalized anxiety disorder (GAD). The purpose of this study was to identify and characterize inflammatory biomarkers in the diagnosis of GAD based on machine learning algorithms. The evaluation of peripheral immune parameters and lymphocyte subsets was performed on patients with GAD. Multivariable linear regression was used to explore the association between lymphocyte subsets and the of severity GAD. Receiver operator characteristic (ROC) analysis was used to determine the predictive value of these immunological parameters for GAD. Machine learning technology was applied to classify the collected data from patients in the GAD and healthy control groups. Of the 340 patients enrolled, 171 were GAD patients and 169 were non-GAD patients as healthy control. The levels of neutrophil (NEU), monocytes (MON) and systemic immune-inflammation index (SII) were significantly elevated in GAD patients (P<0.01), and the count and proportion of immune cells, including CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells and CD3-CD16+CD56+ NK cells (P<0.001) have undergone large changes. The classification analysis conducted by machine learning using a weighted ensemble-L2 algorithm demonstrated an accuracy of 95.00±2.04% in assessing the predictive value of these lymphocyte subsets in GAD. In addition, the feature importance analysis score is 0.255, which was much more predictive of GAD severity than for other lymphocyte subsets. In the presented work, we show the level of lymphocyte subsets altered in GAD. Lymphocyte subsets, specifically CD3+CD4+ T %, can serve as neuroinflammatory biomarkers for GAD diagnostics. Furthermore, the application of machine learning offers a highly efficient approach for investigating neuroinflammatory biomarkers and predicting GAD. Our research has provided novel insights into the involvement of cellular immunity in GAD and highlighted the potential predictive value and therapeutic targets of lymphocyte subsets in this disorder.

Effects of Shenqi Xiangyi granules in advanced gastric cancer chemotherapy.

Owing to the absence of specific symptoms in early-stage gastric cancer, most patients are diagnosed at intermediate or advanced stages. As a result, treatment often shifts from surgery to other therapies, with chemotherapy and targeted therapies being the primary options for advanced gastric cancer treatment. To investigate both treatment efficacy and immune modulation. A total of 116 patients with advanced gastric cancer, admitted from January 2021 to December 2023, were selected and divided into two groups of 58 each using the random number table method. The control group received FOLFOX4 chemotherapy (oxaliplatin + calcium + folinate + 5-fluorouracil) combined with intravenous sindilizumab. The observation group received the same treatment as the control group, supplemented by oral administration of Senqi Shiyiwei granules. Both groups underwent treatment cycles of 3 weeks, with a minimum of two cycles. The therapeutic efficacy, immune mechanisms, and treatment-related toxicity and side effects were compared between the groups. The objective remission rate in the observation group (55.17%) was higher than that of the control group (36.21%) (P < 0.05). After two treatment cycle, CD3+, CD4+, and CD4+/CD8+ levels were higher in the observation group compared to the control group, while CD8+, regulatory T cells, and natural killer cells were lower (P < 0.05). Additionally, the incidence of leukopenia, nausea, and vomiting was lower in observed group (P < 0.05). No significant differences were observed in the incidence of other adverse reactions (P > 0.05). Adjuvant therapy with Shenqixian granules may enhance the efficacy of simudizumab combined with FOLFOX4 chemotherapy in advanced gastric cancer and the immune function by increasing immune cell counts, making it a valuable option in clinical treatment.

Characterization of liver, adipose, and fecal microbiome in obese patients with MASLD: links with disease severity and metabolic dysfunction parameters

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a range of histological findings from the generally benign simple steatosis to steatohepatitis (MASH) which can progress to fibrosis and cirrhosis. Several factors, including the microbiome, may contribute to disease progression.ResultsHere, we demonstrate links between the presence and abundance of specific bacteria in the adipose and liver tissues, inflammatory genes, immune cell responses, and disease severity. Overall, in MASLD patients, we observed a generalized obesity-induced translocation of gut bacteria to hepatic and adipose tissues. We identified microbial patterns unique to more severely diseased tissues. Specifically, Enterococcus, Granulicatella, and Morganellaceae abundance is positively correlated with immune cell counts and inflammatory gene expression levels, and both genera are significantly enriched in MASH patients. Brevibacterium is enriched in adipose tissues of patients with liver fibrosis.ConclusionTogether, these results provide further insight into the microbial factors that may be driving disease severity.5gz9zWLTQ4ZzRXZ3CTt_7qVideo

Sex hormone-dependent host-microbiome interactions and cardiovascular risk (XCVD): design of a longitudinal multi-omics cohort study

IntroductionCardiovascular diseases (CVDs) present differently in women and men, influenced by host-microbiome interactions. The roles of sex hormones in CVD outcomes and gut microbiome in modifying these effects are poorly...

Causal Relationship Between Intestinal Microbiota, Inflammatory Cytokines, Peripheral Immune Cells, Plasma Metabolome and Parkinson's Disease: A Mediation Mendelian Randomization Study.

Parkinson's disease (PD) is a neurodegenerative disease involving multiple factors. We explored the connection between intestinal microbiome levels and PD by examining inflammatory cytokines, peripheral immune cell counts and plasma metabolomics as potential factors. By obtaining the Genome-Wide Association Study (GWAS) data needed for this study from GWAS Catalog, including summary data for 473 intestinal microbiota traits (N = 5959), 91 inflammatory cytokine traits (N = 14,824), 118 peripheral immune cell count traits (N = 3757), 1400 plasma metabolite traits (N = 8299) and PD traits (N = 482,730). We used two-step Mendelian randomization (MR) mediated analysis to investigate possible pathways from intestinal microbiota to PD mediated by inflammatory cytokines, peripheral immune cells and plasma metabolites. MR has revealed the causal effects of 19 intestinal microbiota, 1 inflammatory cytokine and 12 plasma metabolites on PD, whereas there is no significant causal relationship between immune cell count characteristics and the occurrence of PD. Mediation analysis showed that the associations between the genus Demequina and PD were mediated by tryptophan with mediated proportions of 17.51% (p = 0.0393). Our study demonstrates that genus Demequina may promote the occurrence of PD by reducing the levels of tryptophan.

Causal role of immune cells in IgA nephropathy: a mendelian randomization study

Background Previous observational studies have shown that immune cells play an important role in IgA nephropathy. However, the specific causal relationship between the two is inconsistent. Methods We used a two-sample mendelian randomization(MR) analysis to investigate the causal association between 731 immune cell signatures and IgA nephropathy in this study. Based on published GWAS data, immune cells were characterized by four immune types absolute cell (AC) counts, median fluorescence intensity (MFI), morphological parameters (MP), relative cell (RC) counts. Meanwhile, heterogeneity test, horizontal pleiotropy and sensitivity test were used to evaluate the robustness and reliability of the results. Results An important causal association was achieved for 14 RC traits/IgA nephropathy, 3 AC traits/IgA nephropathy, 10 MFI traits/IgA nephropathy, and 1 MP trait/IgA nephropathy. However, after false discovery rate (FDR) correction, only one immunophenotype was found to be protective against IgA nephropathy. The OR of herpesvirus entry mediator (HVEM) on terminally differentiated CD4+ T cell (maturation stages of T-cell panel) on IgA nephropathy risk was estimated to be 0.727 (95%CI: 0.624-0.847, p = 4.20e − 05, PFDR = 0.023) according to inverse variance weighting (IVW) method, and the weighted-median method yielded similar results (OR = 0.743, 95% CI: 0.596-0.927, p = 0.008). Although not statistically significant, the association was consistent with MR-Egger, simple mode and weighted mode. Conclusions Our study further confirmed that immune cells play a complex and important role in the pathogenesis of IgA nephropathy, providing evidence for clinical research.

Mediating role of immune cells in association between volatile organic compounds and periodontitis: NHANES 2011-2014.

The relationship between humans and volatile organic compounds (VOCs) is a persistent concern due to their widespread sources and high evaporation rates. However, there is currently limited direct evidence linking VOC exposure to the development of periodontitis. This cross-sectional study analyzed 1525 participants and 21 urinary VOCs in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, aiming to investigate the relationship between periodontitis risk, assessed by attachment loss (AL) and probing depth (PD) and individual VOCs using logistic regression, quantile regression, and subgroup analysis. Weighted quantile sum analysis (WQS) and subgroup analysis were utilized to evaluate whether VOC mixtures were associated with periodontitis risk. Multiple linear regression models were used to examine the association between VOC co-exposure and peripheral immune cell counts. A mediation analysis was performed to evaluate whether peripheral immune cells are involved in the effect of VOC co-exposure on periodontitis prevalence. Urinary levels of 2-aminothiazoline-4-carboxylic acid, mandelic acid, and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine were positively associated with the risk of periodontitis after adjusting for all covariates. The WQS models demonstrated a positive correlation between the mixture of VOCs and the risk of periodontitis, wherein 2-aminothiazoline-4-carboxylic acid emerged as the most important contributor. The mediation analysis suggested that monocytes may play a role in the observed association between VOC co-exposure and the prevalence of periodontitis. Exposure to VOCs is associated with a greater prevalence of periodontitis. Monocytes' mediating role plays a crucial function in the association between the risk of periodontitis and co-exposure to VOCs. Volatile organic compounds (VOCs) are chemicals that evaporate quickly and are found all around us-from paints to cleaning products. Understanding how these compounds affect our health is crucial, especially regarding conditions like periodontitis, a common oral chronic inflammatory disease. In our study, we looked at urine samples from 1525 people who participated in a national health survey between 2011 and 2014 to find out if there is an association between VOC exposure and the risk of developing periodontitis. We found that certain chemicals in the urine, which show VOC exposure, were indeed associated with a greater risk of the disease. We further investigated the collective impact of these VOCs on the risk of periodontitis, revealing that certain chemicals exert a more significant influence than their counterparts. Additionally, our research hints at a potential role for monocytes in the interplay between VOCs and the risk of periodontitis. Our data suggest that exposure to VOCs could be associated with a greater likelihood of periodontitis, with monocytes potentially playing a role in this relationship. This study helps us better understand the potential health impacts of daily chemical exposure and underscores the importance of investigating further how our environment affects our health.

Immune inflammation markers and physical fitness during a congested match play period in elite male soccer players

Background/ObjectiveCellular immune markers of inflammation such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune inflammation index (SII) are frequently used in patient care. The adoption of these markers to elite sports, e.g. soccer could be beneficial when monitoring training and aiming to maximize physical fitness. This study investigated cellular immune inflammation markers and physical fitness in elite male soccer players in relation to changes in training and match exposure during a congested match play period.MethodsFifteen elite male soccer players were evaluated three times (T1, T2, and T3) over 12 weeks (T1–T2: six weeks uncongested period of match play and T2–T3: six weeks congested period of match play). Players performed vertical jump tests (squat jumps [SJ], countermovement jumps [CMJ]), the 20-meter sprint test, and the Yo-Yo intermittent recovery test (YYIRL1) at T1, T2 and T3. Measurements included counts of leucocytes and its subtypes, as well as platelets. Cellular immune inflammation markers (NLR, PLR and SII) were calculatedat T1, T2, and T3. Training session rating of perceived exertion was also recorded on a daily basis.ResultsSignificant increases in leucocyte, neutrophil, eosinophil, basophil and monocyte counts occurred at T3 compared with T2 (0.002 < p < 0.04, -0.56 < ES < -0.40) and T1 (-0.78 < ES < -0.49). Lymphocyte counts were lower at T3 as compared to T2 and T1 (p = 0.038, -0.48 < ES <-0.25), while NLR, PLR and SII were greater at T3 compared to T2 (0.001 < p < 0.015, -1.01 < ES < -0.44) and T1 (-0.99 < ES < -0.21). There was a negative correlation between YYIRL1 performance with NLR (r= -0.56; p = 0.02), PLR (r=-0,44, p = 0.015), and SII (r= -0.63; p = 0.01) after the congested period of match play (i.e., T3). Values for maximal oxygen uptake (VO2max), estimated from the YYIRL1 test, negatively correlated with NLR (r= -0.56; p = 0.02), PLR (r=-0,44, p = 0.015), and SII (p = 0.01; r= -0.63). There was a positive correlation between NLR, and SII with workload parameters. In addition, a clear positive correlation was observed between NLR and SII with competitive loadinstead (r= [0.59–0.64; p˂ 0.001), training load (TL) (r= [0.65–0.68]; p˂ 0.001), session rating of perceived exertion (S-RPE) (r= [0.65–0.68]; p = 0.001), and training volume (r= [0.60–0.61; p = 0.001).ConclusionAn intensive period of congested match play significantly alterated immune cell counts and cellular markers of inflammation (NLR, PLR and SII). Changes in NLR and SII were related to workload parameters, suggesting the usefulness of these markers in regulating training intensity and competitive load. An association between physical fitness (YYIRL1, VO2max) and NLR, PLR and SII suggests that these biomarkers are promising tools to monitor aerobic physical fitness of elite soccer players during congested periods of match play.

Altered Immune Cell Profiles in the Follicular Fluid of Patients with Poor Ovarian Response According to the POSEIDON Criteria.

This study aims to investigate alterations in immune cell counts within preovulatory follicles of patients with poor ovarian response (POR) during assisted reproductive technology (ART), classified according to the POSEIDON criteria. This single-centre cross-sectional study included 543 women undergoing IVF/ICSI treatment, selected based on specific inclusion and exclusion criteria: 292 with normal ovarian response and 251 with poor response. Follicular fluid (FF) was collected on the day of oocyte retrieval and analysed by flow cytometry to determine the proportions of macrophages (Mφs), M1 and M2 Mφs, T cells (CD4 and CD8 T cells), dendritic cells (DCs), including type 1 conventional dendritic cells (cDC1) and type 2 conventional dendritic cells (cDC2), and neutrophils. Multivariable logistic regression assessed the relationship between immune cell counts and POR, Pearson correlation determined associations with the number of retrieved oocytes, and receiver operating characteristic (ROC) curves evaluated the predictive power of immune cell counts for POR. Immune cells accounted for 52.57% (±23.90%) of the total cell population in the follicular microenvironment, which was approximately equal to that of granulosa cells, with Mφs being the most abundant, followed sequentially by T cells, DCs, and neutrophils. In patients with POR, overall Mφs infiltration in the follicular microenvironment decreased, whereas M1 and M2 polarization increased. T cell infiltration increased, with a decrease in the CD4/CD8 ratio. Both cDC1 and cDC2 were significantly elevated. Moreover, multivariable logistic regression revealed that the total macrophage count, CD4 T cell count, and cDC2 count were independent predictors of POR. Notably, cDC2 showed the largest area under the ROC curve, suggesting its strong potential as a biomarker for predicting POR. The proportion of immune cells in preovulatory follicles were significantly altered in patients with POR. These findings suggest that immune cell dynamics in the follicular microenvironment may play a crucial role in determining ovarian response and prognosis, indicating that targeted immunomodulatory strategies could be considered in future therapeutic approaches.

The immune cells causative role in lung cancer: Mendelian randomization study

BackgroundsLung cancer (LC) is the leading cause of cancer-related deaths in China, with its incidence and mortality rates rising annually. Various studies have demonstrated disparities in immune cell counts and profiles between LC patients and healthy individuals. However, the existence of a causal link remains largely uncertain. To explore the potential causal association between immune cells and LC risk, a Mendelian randomization (MR) approach was employed.MethodsEmploying immune cell genome-wide association study (GWAS) data from a public database (n = 731 subjects) and Lung Cancer Genome Research Consortium's GWAS dataset (n = 492,803 participants), unconventional genetic loci remarkably associated with the significant abundance of 731 types of immune cells were extracted according to preset threshold points as instrumental variables. The primarily analytical strategy involved the inverse variance weighting (IVW) method, with the effect size estimates expressed as odds ratio (OR) and 95% CI. The robustness of the findings was assessed through a leave-one-out sensitivity analysis, heterogeneity test, horizontal gene pleiotropy test, MR-PRESSO and MR-Egger.ResultsThe MR analysis identified a significant association between 18 distinct immune cell types and lung cancer risk. MR analysis revealed that 7 types of immune cells, including CD20 on IgD − CD38 − B cell, CD20 on switched memory B cell, IgD on IgD + CD24 + B cell, BAFF − R on IgD − CD38 + B cell, CD39 + resting CD4 regulatory T cell Absolute Count, CD127 on CD45RA + CD4 + T cell, CD8 on Effector Memory CD8 + T cell, displayed a protective effect against lung cancer development. Conversely, 11 other immune cells populations were positive associated with an increased lung cancer risk. In contrast, reverse MR analysis indicated that the lung cancer risk was linked to 11 immune cells, with 2 types of immune cells (CD25 on IgD − CD27 − B cell, CD4 + T cell %leukocyte) showing a are positive correlation with cancer development, whereas 9 types of immune cells appeared to be inversely regulated. These findings collectively imply that specific immune cell populations may play critical roles in either promoting or suppressing the initiation and progression of lung cancer.ConclusionThe findings of this study offer fresh insights into the underlying biological mechanisms governing lung cancer development, thereby opening new avenues for future research in the domain of LC. The identification of specific immune cell subsets with protective or promoting roles provides crucial leads for preventive and therapeutic strategies. These insights have the potential to enhance early detection methods and inform the development of more effective treatment approaches, ultimately benefiting patient outcomes and improving the overall management of lung cancer.

Current and emerging tools for simultaneous assessment of infection and rejection risk in transplantation.

Infection and rejection are major complications that impact transplant longevity and recipient survival. Balancing their risks is a significant challenge for clinicians. Current strategies aimed at interrogating the degree of immune deficiency or activation and their attendant risks of infection and rejection are imprecise. These include immune (cell counts, function and subsets, immunoglobulin levels) and non-immune (drug levels, viral loads) markers. The shared risk factors between infection and rejection and the bidirectional and intricate relationship between both entities further complicate transplant recipient care and decision-making. Understanding the dynamic changes in the underlying net state of immunity and the overall risk of both complications in parallel is key to optimizing outcomes. The allograft biopsy is the current gold standard for the diagnosis of rejection but is associated with inherent risks that warrant careful consideration. Several biomarkers, in particular, donor derived cell-free-DNA and urinary chemokines (CXCL9 and CXCL10), show significant promise in improving subclinical and clinical rejection risk prediction, which may reduce the need for allograft biopsies in some situations. Integrating conventional and emerging risk assessment tools can help stratify the individual's short- and longer-term infection and rejection risks in parallel. Individuals identified as having a low risk of rejection may tolerate immunosuppression wean to reduce medication-related toxicity. Serial monitoring following immunosuppression reduction or escalation with minimally invasive tools can help mitigate infection and rejection risks and allow for timely diagnosis and treatment of these complications, ultimately improving allograft and patient outcomes.

Peripheral Blood Leukocyte Subpopulation Changes in Reaction to an Acute Psychosocial Stressor as Compared to an Active Placebo-Stressor in Healthy Young Males: Mediating Effects of Major Stress-Reactive Endocrine Parameters.

Psychosocial stress has been proposed to induce a redistribution of immune cells, but a comparison with an active placebo-psychosocial stress control condition is lacking so far. We investigated immune cell redistribution due to psychosocial stress compared to that resulting from an active placebo-psychosocial stress but otherwise identical control condition. Moreover, we tested for mediating effects of endocrine parameters and blood volume changes. The final study sample comprised 64 healthy young men who underwent either a psychosocial stress condition (Trier Social Stress Test; TSST; n = 38) or an active placebo-psychosocial stress control condition (PlacTSST; n = 26). Immune cell counts and hemoglobin, epinephrine, norepinephrine, ACTH, renin, and aldosterone levels, as well as those of saliva cortisol, were determined before and up to 30 min after the TSST/PlacTSST. The TSST induced greater increases in total leukocyte, monocyte, and lymphocyte levels as compared to the PlacTSST (p's ≤ 0.001), but in not granulocyte counts. Neutrophil granulocyte counts increased in reaction to both the TSST and PlacTSST (p's ≤ 0.001), while eosinophil and basophil granulocyte counts did not. The psychosocial stress-induced increases in immune cell counts from baseline to peak (i.e., +1 min after TSST cessation) were independently mediated by parallel increases in epinephrine (ab's ≤ -0.43; 95% CIs [LLs ≤ -0.66; ULs ≤ -0.09]). Subsequent decreases in immune cell counts from +1 min to +10 min after psychosocial stress cessation were mediated by parallel epinephrine, renin, and blood volume decreases (ab's ≥ 0.17; 95% CIs [LLs ≥ 0.02; ULs ≥ 0.35]). Our findings indicate that psychosocial stress specifically induces immune cell count increases in most leukocyte subpopulations that are not secondary to the physical or cognitive demands of the stress task. Increases in the number of circulating neutrophil granulocytes, however, are not psychosocial stress-specific and even occur in situations with a low probability of threat or harm. Our findings point to a major role of epinephrine in mediating stress-induced immune cell count increases and of epinephrine, renin, and blood volume changes in mediating subsequent immune cell count decreases from +1 min to +10 min after psychosocial stress cessation.

Abstract 4138606: Toll-like Receptor 4 Signaling Establishes Trained Innate Immunity Through Interferon-Mediated Epigenetic Modifications Leading to Cardioprotection in a Stress-induced Cardiomyopathy Model

Introduction: The mechanisms responsible for establishing preconditioning-induced cardioprotection remain unknown. We have shown that a high dose of isoproterenol (ISO) induces cardioprotection against a second ISO dose in mice. The durability of protection and the lack of an innate immune response suggests trained immunity as a novel cardioprotective mechanism. Hypothesis: We hypothesize that cardioprotection is conferred through trained immunity, by interferon signaling downstream of necrotic cardiac material-mediated Toll-like receptor 4 (TLR4) activation. Methods: Wild-type C57BL/6J mice were intraperitoneally injected with TLR agonists or diluent, and challenged with 300 mg/kg ISO 7 days later. Mice were assessed by 2-D echocardiography, serum cardiac troponin levels, flow cytometry immune cell counts, and Multiome (single nuclei RNA+ATAC) sequencing. Results: The TLR4 agonist lipopolysaccharide (LPS) induced cardioprotection against ISO injury, with mice having enhanced survival (P=0.049) and no changes in cardiac troponin levels (P&gt;0.99), cardiac neutrophil influx (P&gt;0.99) or left ventricular motion (P=0.057) relative to baseline values before injury. Treating LPS-injected mice with β-glucan reversed the effects of LPS on immune cells and abolished cardioprotection. Multiome analysis of genes linked to chromatin peaks with increased accessibility in LPS+vehicle (protected) compared to LPS+β-glucan and diluent control (non-protected) hearts revealed the interferon pathway to be up-regulated across all major cell types. Modulation of interferon signaling with monoclonal antibodies against type 1+2 interferon receptors abolished cardioprotection in LPS-treated mice, whereas pre-treatment with recombinant type 1+2 interferons induced cardioprotection. Importantly, interferon-treated hearts shared similar chromatin accessibility features and enriched transcription factor motifs, including interferon-specific motifs, with LPS-protected hearts across cell types, particularly among non-cardiomyocytes. Conclusions: TLR4-induced interferon signaling is sufficient and in part necessary for cardioprotection against ISO injury. Moreover, our findings show that epigenetic modifications downstream of interferon signaling lead to cardioprotection consistent with trained innate immunity.

Trajectory clustering of immune cells and its association with clinical outcomes after aneurysmal subarachnoid hemorrhage.

The immune response following aneurysmal subarachnoid hemorrhage (aSAH) can exacerbate secondary brain injury and impact clinical outcomes. As the immune response after aSAH is a dynamic process, we aim to track and characterize immune cell trajectories over time to identify patterns associated with various clinical outcomes. In this retrospective single-center study of patients with aSAH, we analyzed immune cell count trajectories, including neutrophil, monocyte, and lymphocyte counts, collected from day 1 to day 14. These trajectories were classified into four distinct clusters utilizing the k-means longitudinal clustering method. A comprehensive multivariable analysis was performed to explore the associations of these immune cell clusters with various clinical outcomes. These outcomes included a Modified Rankin Scale score (mRS) of 3 to 6, indicative of poor functional outcomes, along with complications including shunt dependency, vasospasm, and secondary cerebral infarction. In this study, 304 patients with aSAH were analyzed. The trajectories of immune cell counts, including neutrophils, monocytes, and lymphocytes, were successfully categorized into four distinct clusters for each immune cell type. Within neutrophil clusters, both persistent neutrophilia and progressive neutrophilia were associated with poor functional outcomes, shunt dependency, and vasospasm, with resolving neutrophilia showing a lesser degree of these associations. Within monocyte clusters, early monocytosis was associated with vasospasm, whereas delayed monocytosis was associated with shunt dependency. Within lymphocyte clusters, both early transient lymphopenia and early prolonged lymphopenia were associated with poor functional outcomes. Our study demonstrates that distinct immune cell trajectories post-aSAH, identified through unsupervised clustering, are significantly associated with specific clinical outcomes. Understanding these dynamic immune responses may provide key insights with potential for future therapeutic strategies.

A novel exosome-like nanovesicles from Cordyceps militaris potentiate immunomodulatory and anti-tumor effect by reprogramming macrophages

AimsFungi-derived exosome-like nanovesicles (ENs) are emerging as a highly promising class of nanoparticles, particularly noted for their cost-effective production. However, their impact on immune regulation and their potential as anti-tumor agents need further exploration. Our study specifically focused on the investigation of the immunomodulatory and anti-tumor properties of ENs derived from Cordyceps militaris, an edible fungus that had achieved large-scale commercial production, referred to as CMDENs. Main methodsThe ENs of C. militaris were collected through ultra-high-speed centrifugation, followed by characterization of their physicochemical properties and contents. Subsequently, the biological distribution of these vesicles was investigated using in vivo fluorescence imaging experiments. Finally, the immune activation and polarization of macrophages were examined through both in vitro and in vivo experiments. Key findingsHerein, we presented the discovery of CMDENs that were rich in proteins, lipids, flavonoids and alkaloids. Immunomodulatory experiments conducted in vivo demonstrated that CMDENs exhibited protective effects against cyclophosphamide-induced immunosuppression in mice by significantly enhancing macrophage phagocytosis and peripheral blood immune cell counts. Moreover, CMDENs effectively induced the polarization of M0- and M2-like macrophages toward M1-like phenotype by activating MAPKs signaling pathway. Notably, CMDENs exhibited remarkable capabilities in inhibiting tumor growth by reprogramming tumor-associated macrophages and activating tumor-infiltrating T lymphocytes, without any observed toxicity in mice bearing tumors. SignificanceOur research suggested that CMDENs possessed the potential to be explored as a nano-immunomodulatory agent for cancer.