Systemic Immune Responses Research Articles

The impact of gut microbiota in full-term pregnant women on immune regulation during pregnancy: A prospective, exploratory study.

This study aims to investigate the correlation between gut microbiota and both placental local immune function and the maternal systemic immune system in pregnant women. Twenty-six pregnant women were included in this study, utilizing high-throughput sequencing for gut microbiota analysis. Immune cells and cytokine levels were measured in placental tissue and peripheral venous blood. Integration of gut microbiota data with immune parameters was performed using R, and network correlation analysis was conducted with Cytoscape software. In placental tissues, gut microbiota predominantly influences B lymphocytes (CD3-CD19+/CD3-), indicating a potential bidirectional regulatory role. The impact on CD56+CD16+/CD56+CD16- and CD4+/CD8+ ratios appear minor. Notably, a significant positive correlation was observed between gut microbiota and the placental cytokine interleukin (IL)-5. In peripheral blood, gut microbiota was primarily associated with negative regulation of peripheral B lymphocytes and positive regulation of peripheral Treg cells. Minimal effects are observed on peripheral macrophages and NK cell subtypes. The most substantial impact on peripheral immune balance was reflected in the CD4+/CD8+ ratio, showing a predominant negative correlation, while the influence on the CD56+CD16+/CD56+CD16- ratio is minimal. A significant negative correlation was found between gut microbiota and peripheral cytokines IL-1 and IL-18, while the interaction with the peripheral interferon-γ/IL-4 ratio appears relatively less pronounced. The close correlation between gut microbiota and placental local immune function, as well as maternal systemic immune responses, is evident. This study contributes to a preliminary understanding of the immunomodulatory relationship of gut microbiota during pregnancy.

Modulation of the central nervous system immune response and neuroinflammation via Wnt signaling in health and neurodegenerative diseases

AbstractThe immune response in the central nervous system (CNS) is a highly specialized and tightly regulated process essential for maintaining neural health and protecting against pathogens and injuries. The primary immune cells within the CNS include microglia, astrocytes, T cells, and B cells. They work together, continuously monitor the CNS environment for signs of infection, injury, or disease, and respond by phagocytosing debris, releasing cytokines, and recruiting other immune cells. In addition to providing neuroprotection, these immune responses must be carefully balanced to prevent excessive inflammation that can lead to neuronal damage and contribute to neurodegenerative diseases. Dysregulated immune responses in the CNS are implicated in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Wnt signaling is a crucial pathway in the CNS that regulates various cellular processes critical for brain development, function, and maintenance. Despite enhancing immune responses in the health CNS, dysregulated Wnt signaling exacerbates neuroinflammation in the neurodegenerative brains. This review summarized the role of Wnt signaling in regulating immune response under different conditions. We then examined the role of immune response in healthy brains and during the development of neurodegenerative diseases. We also discussed therapeutic intervention in various neurodegenerative diseases through the modulation of the Wnt signaling pathway and neuroinflammation and highlighted challenges and limitations in current clinical trials.

Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma

BackgroundPleural mesothelioma (PM) is a rare cancer with a dismal prognosis. Dual immune checkpoint inhibitors have improved overall survival, but the rate of immune-related adverse events (irAEs) is high. Serum cytokines reflect systemic immune reactions and may serve as biomarkers for irAEs.Patients and methodsPatients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Serum cytokine levels were measured by Bio-Plex Pro Human Cytokine Screening 48-Plex Panel Assay. Correlations between cytokine levels and irAEs were analyzed by generalized linear mixed models to identify potential diagnostic and predictive biomarkers.ResultsHigher levels of MIG, eotaxin, MIP-1α, IP-10, TNF-α, MIP-1β, IL-4, MIF, IL-16, IL-2RA, SCGF.β and PDFG-BB at baseline are associated with increased risk of developing one or more irAEs. In particular, higher baseline levels of MIG are positively associated with thyroiditis and hypophysitis, and elevated levels of IP-10 and MIG to dermatitis. During the course of treatment, higher levels of MIG, eotaxin, MIF, TNF-α, MIP-1β, IL-4 and IL-16 are associated with an ongoing irAE. We found both predictive and diagnostic value of MIF with fatigue and of eotaxin with both colitis and pneumonitis. Higher levels of CTACK is associated with a lower risk of developing hepatitis, both before and after treatment.ConclusionsElevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES.

The Role of Prebiotic, Probiotic, and Synbiotic in Gut Microbiota and Gut Permeability in Children Affected by Air Pollution

Background: Air pollution has been linked with gut microbiota dysbiosis. Ingested environmental pollutants may alter gut microbiota compositions by changing the environment of the gut. Gut microbiota dysbiosis has been observed in children with asthma, linking the possible role of gut microbiota with systemic immune response and asthma. Methods: This paper aims to identify current science on how prebiotics, probiotics, and synbiotics can improve gut microbiota dysbiosis. Results: We reviewed the existing literature related to the role of pre-, pro-, and synbiotics in child health, and the evidence mapping method was chosen as the rapid review to identify gaps in knowledge and future research needs. Conclusion: In conclusion, the current evidence on the role of prebiotics, probiotics, and synbiotics on child health, while limited, showed promising results on the allergy and immunology pathway, including infection prevention for the gastrointestinal and respiratory tract.

Activation of Stimulator of Interferon Genes (STING): Promising Strategy to Overcome Immune Resistance in Prostate Cancer.

Prostate cancer (PCa) is the most frequent and second-lethal cancer among men. Despite considerable efforts to explore treatments like autologous cellular immunotherapy and immune checkpoint inhibitors, their success remains limited. The intricate tumor microenvironment (TME) and its interaction with the immune system pose significant challenges in PCa treatment. Consequently, researchers have directed their focus on augmenting the immune system's anti-tumor response by targeting the STimulator of the Interferon Genes (STING) pathway. The STING pathway is activated when foreign DNA is detected in the cytoplasm of innate immune cells, resulting in the activation of endoplasmic reticulum (ER) STING. This, in turn, triggers an augmentation of signaling, leading to the production of type I interferon (IFN) and other pro-inflammatory cytokines. Numerous studies have demonstrated that activation of the STING pathway induces immune system rejection and targeted elimination of PCa cells. Researchers have been exploring various methods to activate the STING pathway, including the use of bacterial vectors to deliver STING agonists and the combination of radiation therapy with STING agonists. Achieving effective radiation therapy with minimal side effects and optimal anti-tumor immune responses necessitates precise adjustments to radiation dosing and fractionation schedules. This comprehensive review discusses promising findings from studies focusing on activating the STING pathway to combat PCa. The STING pathway exhibits the potential to serve as an effective treatment modality for PCa, offering new hope for improving the lives of those affected by this devastating disease.

Periodontitis Continuum: Antecedents, Triggers, Mediators, and Treatment Strategies.

Periodontitis (PD) is a chronic inflammatory disease of the periodontium characterized by the formation of gingival pockets and gingival recession. The local inflammatory environment can lead to the destruction of the extracellular matrix and subsequent bone loss. The pathophysiology of PD involves interactions between genetic predisposition, lifestyle, environmental factors, the oral microbiota condition, systemic health disorders, innate and adaptive immune responses, and various host defenses. The review highlighted the importance of the oral cavity condition in systemic health. Thus, a correlation between harmful oral microbiota and cardiovascular disease (CVD)/diabetes/ arthritis, etc, progressions through inflammation and bacterial translocation was highlighted. Antecedents increase an individual's risk of developing PD, trigger initiate microbe-host immunologic responses, and mediators sustain inflammatory interactions. Generally, this review explores the antecedents, triggers, and mediators along the pathophysiological continuum of PD. An analysis of modern approaches to treating periodontitis, including antibiotics for systemic and local use, was carried out. The potential role of natural ingredients such as herbal extracts, phytoconstituents, propolis, and probiotics in preventing and treating PD was highlighted.

MULTIMODAL NUCLEAR FACTOR-ERYTHROID-2-RELATED FACTOR (NRF2) THERAPY IN THE CONTEXT OF MAMMALIAN TARGET OF RAPAMYCIN (MTOR) INHIBITION REPROGRAMS THE ACUTE SYSTEMIC AND PULMONARY IMMUNE RESPONSE AFTER COMBINED BURN AND INHALATION INJURY.

Severe burn injuries induce acute and chronic susceptibility to infections, which is largely attributed to a hyper-proinflammatory response followed by a chronic anti-inflammatory response. Concurrent inhalation injury (B + I) causes airway inflammation. Pulmonary macrophages and neutrophils are "hyperactive" with increased reactive oxygen (ROS) and nitrogen species (RONS) activity, but are unable to clear infection, causing airway damage upon activation. Nuclear factor-erythroid-2-related factor (NRF2) is a critical immunomodulatory component that induces compensatory anti-inflammatory pathways when activated. On the other hand, inhibition of mammalian target of rapamycin (mTOR) reduces proinflammatory responses. The therapeutic use of these targets is limited, as known modulators of these pathways are insoluble in saline and require long-term administration. A biocompatible NRF2 agonist (CDDO) and rapamycin (RAPA) poly(lactic-co-glycolic acid) (PLGA) microparticles (MP) were created, which we hypothesized would reduce the acute hyper-inflammatory response in our murine model of B + I injury. BI-injured mice that received CDDO-MP or both CDDO-MP and RAPA-MP (Combo-MP) an hour after injury displayed significant changes in the activation patterns of pulmonary and systemic immune genes and their associated immune pathways 48 h after injury. For example, mice treated with Combo-MP showed a significant reduction in inflammatory gene expression compared to untreated or CDDO-MP-treated mice. We also hypothesized that Combo-MP therapy would acutely decrease bacterial susceptibility after injury. BI-injured mice that received Combo-MP an hour after injury, inoculated 48 h later with Pseudomonas aeruginosa (PAO1), and sacrificed 48 h after infection displayed significantly decreased bacterial counts in the lungs and liver versus untreated B + I mice. This reduction in infection was accompanied by significantly altered lung and plasma cytokine profiles and immune reprogramming of pulmonary and splenic cells. Our findings strongly suggest that multimodal MP-based therapy holds considerable promise for reprogramming the immune response after burn injuries, particularly by mitigating the hyper-inflammatory phase and preventing subsequent susceptibility to infection.

Introducing Degradable Cationic Nanogels Carrying TLR9 Stimulating Oligonucleotides.

Cationic, core-crosslinked nanogel particles are prepared from synthetic biodegradable materials. These fully hydrophilic nanogels offer superior customizability compared to common lipid nanoparticles, thereby circumventing intrinsic immune stimulatory properties. Electrostatic loading allows for complexation of nucleic acids including the immune stimulatory Toll-like receptor 9 (TLR9) agonistCpG-ODN (cytidine-phosphate-guanosine oligodeoxynucleotide). Only when complexed inside nanogels, one can control CpG-ODN's biodistribution, prevent systemic toxicity, and increase bioavailability at target locations. Nanogels are prepared from cyclic aliphatic carbonate monomers with reactive pentafluorophenyl (PFP) esters. First, block copolymers are acquired via cationic ring opening polymerization (CROP) onto polyethylene glycol (PEG). Upon self-assembly in ethanol, the micelles' core is cationically core-crosslinked, and the resulting fully hydrophilic particles exhibit sizes of ≈20nm, also upon loading with CpG-ODN. In vitro, they promote intracellular delivery devoid of carrier-related toxicities, while retaining the immune stimulatory properties of the TLR agonist cargo. In vivo, the nanogels reduce systemic liver immune responses and remain near the injection site. Additionally, delivery into cDC1 (conventional dentritic cells type 1) antigen-presenting cells, which are highly relevant for antitumoral T-cell immune responses, is confirmed. Altogether, cationic, core-crosslinked polycarbonate nanogels show promise for nucleic acid delivery, showcasing controlled immunostimulatory cargo delivery and an enhanced hydrolytic biodegradability profile, highly valuable for cancer immunotherapy.

Layered Double Hydroxides for Radium-223 Targeted Alpha Therapy with Elicitation of the Immune Response.

Targeted Alpha therapy (TAT) has promising application prospects in tumor therapy. It is very appealing to design alpha-emitting radiopharmaceuticals that can modulate the immune microenvironment to overcome the limitations of immunotherapy. Herein, Mg/Al layered double hydroxide nanomaterials (LDH) are utilized to load the alpha-emitting nuclide Radium-223 (223Ra), achieving precise delivery of 223Ra to the tumor microenvironment. Dual-modal imaging is employed to dynamically monitor the in vivo distribution of 223Ra-LDH, ensuring its prolonged retention at the tumor site. In vitro experimentsshowed that ionizing radiation from alpha-emitting nuclides effectively reduced glutathione (GSH) and producedlarge amounts of reactive oxygen species (ROS), which damaged mitochondria and released free calcium (Ca2+), thereby aggravating tumor cell death. Additionally, DNA double-strand breaks induced by alpha-emitting radiation triggered the STING signaling pathway, which in turn effectively induced immunogenic cell death (ICD) and promoted immune cell maturation and activation. The synergistic effect with immunotherapy triggered a powerful systemic antitumor immune response. Overall, this study develops a novel TAT therapeutic strategy with sufficient antitumor immunity.

Study on the physicochemical properties and immune regulatory mechanism of polysaccharide fraction from Aronia Melanocarpa fruit.

Aronia Melanocarpa (Michx.) Elliott fruit has been extensively used in the food and medicinal fields. This study aimed to analyze the physicochemical properties of a polysaccharide fraction (AMP2) isolated from this fruit for the first time and investigated its immune regulatory mechanism. The physicochemical properties of AMP2 were determined using high-performance gel permeation chromatography, PMP derivatization-high performance liquid chromatography, Ultraviolet spectroscopy, and infrared spectroscopy. The metagenomic technology was applied to investigate the regulatory effects and mechanisms of AMP2 on the gut microbiota of immunosuppressed mice. The results showed that molecular weight of AMP2 was 83,444Da, which was mainly composed of D-arabinose, D-xylose, D-mannose, D-rhamnose and D-glucose, and both β-type and α-type glycosidic bonds contained in its structure. AMP2 changed the composition of gut microbiota by increasing the number of beneficial and probiotic bacteria, thereby regulated the intestinal mucosal immune system of host. AMP2 improved intestinal immune system response and antimicrobial capacity through positive regulation of the NOD-like receptor signaling pathway and neutrophil extracellular trap formation. The results demonstrate the potential of AMP2 in immune regulation, providing a new perspective for its subsequent development and contributing to the development and application of related health foods.

318 Non-Segmental Vitiligo in Older Patients is Associated with Increased Activation and Decreased Regulation of the Systemic Immune Response, Independent of Disease Duration

318 Non-Segmental Vitiligo in Older Patients is Associated with Increased Activation and Decreased Regulation of the Systemic Immune Response, Independent of Disease Duration

Fecal Microbiota Transplantation Activity of Floccularia luteovirens Polysaccharides and Their Protective Effect on Cyclophosphamide-Induced Immunosuppression and Intestinal Injury in Mice

Floccularia luteovirens polysaccharides (FLP1s) have potential biological activities. Our previous study showed that FLP1s positively regulated gut immunity and microbiota. However, it is still unclear whether FLP1s mediate gut microbiota in immunosuppressed mice. This research aims to explore the relationship between FLP1-mediated gut microbes and intestinal immunity in immunosuppressed mice through fecal microbiota transplantation (FMT). The results demonstrated that FLP1s exhibited prebiotic and anti-immunosuppressive effects on CTX-induced immunosuppressed mice. FFLP1 treatment (microbiota transplantation from the fecal sample) remarkably elevated the production of sIgA and secretion of the anti-inflammatory cytokines IL-4, TNF-α, and IFN-γ in the intestine of CTX-treated mice, inducing activation of the MAPK pathway. Moreover, FFLP1s mitigated oxidative stress by activating the Nrf2/Keap1 signaling pathway and strengthened the intestinal barrier function by upregulating the expression level of tight junction proteins (occludin, claudin-1, MUC-2, and ZO-1). Furthermore, FFPL1s restored gut dysbiosis in CTX-treated immunosuppressed mice by increasing the abundance of Alloprevotella, Lachnospiraceae, and Bacteroides. They also modified the composition of fecal metabolites, leading to enhanced regulation of lipolysis in adipocytes, the cGMP-PKG pathway, the Rap1 signaling pathway, and ovarian steroidogenesis, as indicated by KEGG pathway analysis. These findings indicate that FLP1s could modulate the response of the intestinal immune system through regulation of the gut microbiota, thus promoting immune activation in CTX-treated immunosuppressed mice. FLP1s can serve as a natural protective agent against CTX-induced immune injury.

The Oxytetracycline and Florfenicol Effect on the Immune System and Oxidative Stress Response of the SHK-1 Cell Line of Salmo salar

The aquaculture industry in Chile, as in the rest of the world, has rapidly grown, becoming a crucial economic sector. However, diseases pose a major threat, causing significant economic losses and environmental impacts. Various antimicrobials, particularly Oxytetracycline and Florfenicol, are used to combat these diseases, which has boosted production and mitigated economic losses. However, excessive antibiotic use has led to pathogen resistance, necessitating higher doses. This overuse can cause side effects in fish, including liver damage and immunosuppression. This study aimed to determine the impact of multiple doses of florfenicol and oxytetracycline on the SHK-11 cell line of Salmo salar by analyzing the expression of genes related to innate immunity and oxidative stress by qRT-PCR in addition to the quantification of immune system proteins via dot blot. The experimental treatments were the following: cells were stimulated with different concentrations of oxytetracycline (0.25, 0.5, and 1.5 µg/mL) and florfenicol (1, 10, and 20 µg/mL) for time kinetics of 0.5, 1, 3, 6, 12, 24, and 48 h. For both cases, controls consisting of cells without antibiotics were included. The expression of the immune system genes was mostly inhibited compared to the control. However, it was observed that TLR-1 and MyD88 present a joint activation pattern at different times and concentrations for both antibiotics. Regarding the expression of CAT and GPx, transcripts were increased in the early stages of stimulation with oxytetracycline and florfenicol, followed by a subsequent decrease in gene expression. This study provides relevant information to understand the effect of antibiotics at the cellular level in one of the most important species for global aquaculture, the Atlantic salmon.

Single-cell transcriptomic profiling of maize cell heterogeneity and systemic immune responses against Puccinia polysora Underw.

Southern corn rust (SCR), caused by Puccinia polysora Underw (P. polysora), is a catastrophic disease affecting maize, leading to significant global yield losses. The disease manifests primarily as pustules on the upper surface of corn leaves, obscuring our understanding of its cellular heterogeneity, the maize's response to its infection and the underlying gene expression regulatory mechanisms. In this study, we dissected the heterogeneity of maize's response to P.polysora infection using single-cell RNA sequencing. We delineated cell-type-specific gene expression alterations in six leaf cell types, creating the inaugural single-cell atlas of a maize leaf under fungal assault. Crucially, by reconstructing cellular trajectories in susceptible line N110 and resistant line R99 during infection, we identified diverse regulatory programs that fortify R99's resistance across different leaf cell types. This research uncovers an immune-like state in R99 leaves, characterized by the expression of various fungi-induced genes in the absence of fungal infection, particularly in guard and epidermal cells. Our findings also highlight the role of the fungi-induced glycoside hydrolase family 18 chitinase 7 protein (ZmChit7) in conferring resistance to P. polysora. Collectively, our results shed light on the mechanisms of maize resistance to fungal pathogens through comparative single-cell transcriptomics, offering a valuable resource for pinpointing novel genes that bolster resistance to P. polysora.

Transcriptomic Profiling Reveals Differences in Slow-Twitch and Fast-Twitch Muscles of a Cigarette Smoke-Exposed Rat Model.

Cigarette smoking is known to affect muscle function and exercise capacity, including muscle fatigue resistance. Most studies showed diminished cross-sectional area and fibre type shifting in slow-twitch muscles such as the soleus, while effects on fast-twitch muscles were seldom reported and the differential responses between muscle types in response to exposureto cigarette smoke (CS) were largely unknown. This study aimed to elucidate the histomorphological, biochemical and transcriptomic changes induced by CS on both slow-twitch and fast-twitch muscles. Male Sprague-Dawley rats were randomly divided into two groups: sham air (SA) and CS. The rats were exposed to CS for 8 weeks using an exposure chamber system to mimic smoking conditions. Histomorphological analyses on muscle fibre type and cross-sectional area were determined in soleus and extensor digitorum longus (EDL). Transcriptomic profiles were investigated for identifying differentially expressed genes (DEGs) and potential mechanistic pathways involved. Inflammatory responses in terms of the macrophage population and the level of inflammatory cytokines were measured. Markers for muscle-specific proteolysis were also examined. Soleus muscle, but not in EDL, exhibited a significant increase in Type IIa fibres (SA: 9.0 ± 3.3%; CS: 19.8 ± 2.4%, p = 0.002) and decrease in Type I fibres (SA: 90.1 ± 3.6%; CS: 77.9 ± 3.3%, p = 0.003) after CS exposure. RNA sequencing revealed 165 identified DEGs in soleus including upregulation of 'Cd68', 'Ccl2' and 'Ucp2' as well as downregulation of 'Ucp3', etc. Pathways enrichment analysis revealed that the upregulated pathways in soleus were related to immune system and cellular response, while the downregulated pathways were related to oxidative metabolism. Only 10 DEGs were identified in EDL with less enriched pathways. The soleus also showed elevated pro-inflammatory cytokines, and the total macrophage marker CD68 was significantly higher in soleus of CS compared to the SA group (CD68+/no. of fibre: SA = 60.3 ± 39.3%; CS = 106.5 ± 27.2%, p = 0.0039), while the two groups in EDL muscle showed no significant difference. The expression of E3 ubiquitin ligase atrogin-1 associated with muscle degradation pathways was 1.63-fold higher in the soleus after CS, while no significant differences were observed in the EDL. The CS-induced inflammatory responses on soleus muscle are likely mediated via targeting mitochondrial-related signalling, resulting in mitochondrial dysfunction and impaired oxidative capacity. The presumably less active mitochondrial-related signalling in EDL renders it less susceptible to changes towards CS, accounting for differential impacts between muscle types.

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.

Viral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses to severe pediatric vLRTI in both the lower airway and systemic circulation. To address this gap, gain insights into vLRTI pathophysiology, and test a novel diagnostic approach, we assayed 1,305 proteins in tracheal aspirate (TA) and plasma from 62 critically ill children using SomaScan. We performed differential expression (DE) and pathway analyses comparing vLRTI (n = 40) to controls with non-infectious acute respiratory failure (n = 22), developed a diagnostic classifier using LASSO regression, and analyzed matched TA and plasma samples. We further investigated the impact of viral load and bacterial coinfection on the proteome. The TA signature of vLRTI was characterized by 200 DE proteins (Padj <0.05) with upregulation of interferons and T cell responses and downregulation of inflammation-modulating proteins including FABP and MIP-5. A nine-protein TA classifier achieved an area under the receiver operator curve (AUC) of 0.96 (95% CI: 0.90-1.00) for identifying vLRTI. In plasma, the host response to vLRTI was more muted with 56 DE proteins. Correlation between TA and plasma was limited, although ISG15 was elevated in both compartments. In bacterial coinfection, we observed increases in the TNF-stimulated protein TSG-6, as well as CRP, and interferon-related proteins. Viral load correlated positively with interferon signaling and negatively with neutrophil-activation pathways. Taken together, our study provides fresh insights into the lower airway and systemic proteome of severe pediatric vLRTI and identifies novel protein biomarkers with diagnostic potential.IMPORTANCEWe describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated a positive correlation with interferon-related protein expression and a negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insights into the lower airway and systemic proteome of severe pediatric vLRTI.

Respiratory delivery of single low-dose nebulized PFCE-C25 NEs for lymphatic transport and durable stimulation of antitumor immunity in lung cancer.

The currently available immune checkpoint inhibitors (ICIs) often fail to achieve the desired clinical outcomes due to inadequate immune activation, particularly in patients with lung cancer. To reverse this situation, we synthesized inhalable PFCE-C25 nanoemulsions (NEs), which target lymphocyte activation genes (LAG-3) on immune cells within tumor microenvironment and tumor-draining lymph nodes (TDLNs). By combining in vivo 19F-MR molecular imaging, we investigate the immunological effects of a single low-dose PFCE-C25 NEs in multiple murine lung cancer models, including human immune system (HIS) mouse models, and validated its immunological effects in human TDLNs. The nebulization therapy with PFCE-C25 NEs demonstrated a notable and enduring maturation of dendritic cells (DCs) in TDLNs, leading to systemic immune responses, prolonged survival, the establishment of immune memory, and resistance to tumor rechallenge. Thus, PFCE-C25 NEs successfully demonstrate a promising and efficient approach for enhancing lymphatic transport and sustained activation of antitumor immune responses in lung cancer.

The Association between Systemic Inflammation and the Prostate Cancer: based on the National Health and Nutrition Examination Survey and Mendelian Randomization Analysis.

The purpose of this combination research was to examine the relationship between systemic inflammation and the risk of prostate cancer (PCa) through the National Health and Nutrition Examination Survey (NHANES) cross-sectional study and two-sample Mendelian randomization (MR) analysis. We incorporated NHANES data spanning the years 2001 to 2010, with exposure as systemic inflammation, evaluated using systemic immune-inflammation index (SII) and outcome as PCa, and performed multivariate logistic regression and restricted cubic spline (RCS) to test the correlation between SII and PCa. Further, two-sample MR was used to identify causal associations between specific immune cells and PCa. A total of 7706 participants (age≥40 years) were included in the analysis in the cross-sectional study, including 350 PCa cases, 7356 controls. Higher SII levels were associated with increased odds of PCa (P<.05). The odds ratio (OR) for PCa was 1.51 (95% CI 1.09-2.08) for the highest versus lowest quartile of SII levels in the fully adjusted model. Also, the RCS analysis showed a threshold effect, with SII levels above 8.90 associated with increased odds of PCa. In addition, MR results suggested a causal relationship between CD62L- monocyte, CD62L- HLA DR+ monocyte, CD14+ CD16+ monocyte, CD62L- Dendritic Cell, Monocytic Myeloid-Derived Suppressor Cell, CD28- CD8dim T cell, CD39+ resting CD4 regulatory T cell and PCa (P<.05). This combination analysis provides evidence for a significant causal relationship between systemic inflammation and PCa risk. These findings highlight systemic inflammation and inflammatory immune responses as potential modifiable risk factors for PCa.

The role of immunoglobins in atherosclerosis development; friends or foe?

Coronary artery disease, atherosclerosis, and its life-threatening sequels impose the hugest burden on the healthcare systems throughout the world. The intricate process of atherosclerosis is considered as an inflammatory-based disorder, and therefore, the components of the immune system are involved in different stages from formation of coronary plaques to its development. One of the major effectors in this way are the antibody producing entities, the B cells. These cells, which play a significant and unique role in responding to different stress, injuries, and infections, contribute differently to the development of atherosclerosis, either inhibitory or promoting, depending on the type of subsets. B cells implicate in both systemic and local immune responses of an atherosclerotic artery by cell-cell contact, cytokine production, and antigen presentation. In particular, natural antibodies bind to oxidized lipoproteins and cellular debris, which are abundant during plaque growth. Logically, any defects in B cells and consequent impairment in antibody production may greatly affect the shaping of the plaque and its clinical outcome. In this comprehensive review, we scrutinize the role of B cells and different classes of antibodies in atherosclerosis progression besides current novel B-cell-based therapeutic approaches that aim to resolve this affliction of mankind.

Intranasal trivalent candidate vaccine induces strong mucosal and systemic immune responses against Neisseria gonorrhoeae

The spread of multidrug-resistant strains of Neisseria gonorrhoeae poses a great challenge in gonorrhea treatment. At present, vaccination is the best strategy for gonorrhea control. However, given the extensive antigenic variability of N. gonorrhoeae, the effectiveness of monovalent vaccines is limited. Therefore, increasing the coverage of vaccination by using a multivalent vaccine may be more effective. In this study, a trivalent vaccine comprising three conserved antigens, namely, the App passenger domain, MetQ, and neisserial heparin binding antigen (NHBA), was constructed, and its protective effect was evaluated. Trivalent vaccines induced stronger circulating IgG and IgA antibody responses in mice than monovalent vaccines, in addition to eliciting Th1, Th2, and Th17 immune responses. Antiserum generated by the trivalent vaccine killed N. gonorrhoeae strains (homologous FA1090 and heterologous FA19), exhibiting superior bactericidal capacity than NHBA and MetQ vaccine antisera against N. gonorrhoeae, but similar capacities to those of the App vaccine antiserum. In addition, the trivalent vaccine antiserum achieved greater inhibition of N. gonorrhoeae FA1090 strain adherence to ME-180 cells compared to that elicited by the monovalent vaccine antiserum. In a mouse vaginal infection model, the trivalent vaccine was modestly effective (9.2% decrease in mean area under curve compared to the pCold-TF control mice), which was somewhat better than the protection seen with the monovalent vaccines. Our findings suggest that recombinant multivalent vaccines targeting N. gonorrhoeae exhibit advantages in protective efficacy compared to monovalent vaccines, and future research on multivalent vaccines should focus on optimizing different antigen combinations.