Influenza is a highly contagious virus with most individuals showing recovery within a week after symptom onset. However, children, the elderly, and those with chronic health conditions are at high risk of developing serious complications. Extensive immune cell infiltration of the lung and massive production of pro-inflammatory cytokines can result in lung tissue damage and disruption, resulting in hypoxia and death. During the 2024-2025 influenza season in the USA, influenza caused an estimated 27,000-130,000 deaths. Our previous studies have shown that agents known to drive polarization of macrophages into the M2a phenotype mitigated inflammatory responses to influenza H1N1 A/PR/8/34 (PR8). Since IRS2 dampens the IL-4-induced differentiation to the M2a subtype, we sought to determine the impact of IRS2 on PR8 infection. Contrary to expectations, IRS2 -/- mice exhibited enhanced susceptibility to PR8 when compared to IRS2 +/+ mice, which was associated with a significant drop in blood oxygen saturation. Additionally, PR8 infection induced significantly greater inflammation in the lungs of IRS2 -/- mice than IRS2 +/+ mice. Conversely, viral replication was not significantly different. Significantly increased levels of the inflammatory mediator HMGB1 and airway epithelial cell denuding were observed in the lungs of IRS2 -/- mice, with a concomitant decrease in M2a gene expression. Mice with myeloid-specific knockout of IRS2 showed no enhanced sensitivity to PR8, supporting the hypothesis that the major impact of IRS2-deficiency on host response to PR8 infection is not myeloid cell-intrinsic. Overall, these results suggest that in the absence of IRS2, airway epithelial cells are especially sensitive to influenza-induced damage through dysregulated inflammation, resulting in increased susceptibility during infection.
Background and Objectives Trained immunity (TI) refers to a non-specific, long-lasting protective immune response that occurs following initial stimulation of the immune system and thought to be largely mediated by functional reprogramming of myeloid cells. TI has been demonstrated in BCG-vaccinated infants and can be induced in human cells and adult mice via agonists of pattern recognition receptors (PRR), such as β-glucan or MDP (a muropeptide that activates NOD2). However, its induction in neonates remains poorly understood. Previously, we demonstrated that the synthetic TLR2-NOD2 dual agonist CL429 enhances antimicrobial functions in adult mice and protects against subsequent infection with Leptospira interrogans , a zoonotic pathogen. We also demonstrated the immediate protective benefits of NOD2 stimulation in neonates against Cryptosporidium, a zoonotic pathogen that affects young animals in livestock herds. However, whether NOD2 agonists can induce TI in neonates and protect them at adulthood is unknown. Methods and Results Here, we investigated whether exposure of neonatal mice to PRR agonists (CL429, MDP or β-glucan), administered intraperitoneally at one week interval at 7/14 or 14/21 days of age, could enhance inflammatory cytokines production after ex vivo restimulation and confer long-term protection into adulthood. Surprisingly, none of the treatments enhanced ex vivo cytokine responses in adulthood after restimulation, nor did they confer protection against experimental leptospirosis. Instead, MDP-treated neonates exhibited 50% mortality following adult infection, revealing an unexpected detrimental effect. Conclusion These findings demonstrate that these PRR agonists fail to induce protective TI against Leptospira when administered to neonatal mice, challenging assumptions derived from adult models. Furthermore, our study reveals the risks of administering immunostimulants during the early stages of life, and highlights unanticipated and potentially harmful, PRR- and age-specific mechanisms of immune system modulation.
Dendritic cells (DCs) orchestrate antitumor immunity by integrating signals from the tumor microenvironment to prime effective T cell responses. Many tumors display altered glycosylation patterns, including tumor-associated carbohydrate antigens (TACAs) such as the Tn antigen (GalNAcα1- O -Ser/Thr); yet how these structures influence DC function is not well defined. Here, we investigated how Tn-bearing glycoconjugates modulate DC activation and shape adaptive immunity. Bone marrow-derived DCs (BMDCs) efficiently internalized fluorescently labeled Tn-glycoconjugates, whereas uptake of non-glycosylated counterparts was negligible. Although Tn-glycoconjugates alone did not induce DC maturation, co-stimulation with the Toll-like receptor 9 (TLR9) agonist CpG markedly increased CD86 expression and the secretion of IL-12/23p40 and IL-6, with the multivalent construct MAG:Tn3-PV eliciting the strongest response. These conditioned BMDCs promoted strong IFN-γ production by allogeneic splenocytes, consistent with a Th1-polarizing phenotype. Mechanistically, both uptake and CpG-enhanced activation required the C-type lectin receptor MGL2, as blockade of MGL or competition with GalNAc abrogated glycoconjugate uptake and CpG-enhanced cytokine induction. Pharmacological inhibition revealed that MGL2 signaling synergizes with TLR9 through the Syk–Raf-1–NF-κB axis. In vivo , mice immunized with DCs conditioned with Tn-glycoconjugate- plus CpG displayed enhanced splenocyte proliferation, increased IFN-γ secretion, and elevated cytotoxic activity without IL-10 induction, confirming a Th1-skewed response. Collectively, these findings identify MGL2 as a critical mediator of Tn-glycoconjugate sensing and unveil a synergistic C-type lectin receptor (CLR)–TLR9 cross-talk that amplifies DC maturation and cytotoxic immunity. This study provides mechanistic insight into how specific glycan–lectin interactions fine-tune innate receptor signaling, highlighting the potential of Tn-based glycoconjugates as immunomodulatory tools for vaccine design and cancer immunotherapy.
Introduction Lupus nephritis (LN) is characterized by significant heterogeneity and a complex pathophysiology, which traditional methods struggle to fully resolve. Advanced multi-omics approaches are essential to disentangle its cellular and molecular drivers. Methods We employed an integrative strategy combining single-cell RNA sequencing (scRNA-seq) profiling of LN biopsies with large-scale bulk RNA-seq cohorts. We applied non-negative matrix factorization (NMF) to scRNA-seq data to define robust immune meta-programs and utilized CellChat to decode cell-cell communication networks. Leveraging these insights to overcome sample size limitations, we prioritized key pathways and developed 399 machine learning predictive models using bulk transcriptomics, validated on independent cohorts. Results ScRNA-seq analysis revealed a distinct cellular landscape, including a rare population of plasmacytoid dendritic cells (pDCs) and an expanded population of CD56dimCD16 + natural killer (NK) cells expressing high levels of IFN-γ and perforin, suggesting a role in inflammatory pathology. Macrophage subpopulation CM2 emerged as a central pro-inflammatory hub, potentially driving fibrosis via autocrine signaling and epithelial activation. We observed reduced Treg-B cell interactions, suggesting a regulatory collapse. Our machine learning models, based on innate immunity, circadian rhythms, apoptosis, and NF-κB signaling, achieved high diagnostic accuracy (AUC = 0.929 for innate immunity). Hub genes, including CYBB , CSF2RB , and IRF8 , were confirmed to be upregulated in LN and correlated with clinical severity in external validation datasets. Molecular docking simulations suggested a potential structural basis for CYBB-dexamethasone interaction, providing a hypothesis for future verification. Discussion This study identifies CM2 macrophages and dysregulated pDC-NK axes as key drivers of LN. By bridging cellular interactomes with clinical predictive modeling, we provide a robust roadmap for precision detection and identifying potential therapeutic targets in LN.
Background Trained immunity, a form of long-term functional reprogramming of innate immune cells through epigenetic and metabolic changes, traditionally confers protection against infections. However, inappropriate activation by endogenous sterile stimuli can drive persistent maladaptive inflammation in non-communicable diseases (NCDs). Objective This systematic review synthesizes primary evidence for trained immunity in atherosclerosis, type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and neurodegenerative disorders, focusing on endogenous inducers, cellular mediators, mechanisms, and translational implications. Data Sources and Methods Following PRISMA guidelines, we included original studies demonstrating trained immunity induced by sterile endogenous signals in the targeted diseases. Narrative synthesis was performed due to heterogeneity precluding meta-analysis. Results Twelve primary studies met the inclusion criteria. In atherosclerosis (n = 8 studies), oxLDL, aldosterone, Western diet lipids, and post-myocardial infarction signals induced trained immunity in monocytes or macrophages and hematopoietic progenitors via H3K4me3 enrichment, mTOR/NLRP3 activation, and glycolytic/fatty acid shifts, leading to persistent cytokine hyperproduction (TNF-α, IL-6), foam cell formation, and transmissible plaque progression. In T2DM/hyperglycemia (n = 3), high glucose levels triggered MLL-mediated epigenetic reprogramming and glycolysis-dependent “metabolic memory,” which skewed myelopoiesis and accelerated atherosclerosis despite normoglycemia. In CKD (n = 1), indoxyl sulfate induced AhR-dependent arachidonic acid pathway activation with metabolic rewiring, sustaining systemic inflammation. In neurodegeneration (n = 1), peripheral stimuli caused epigenetic reprogramming in microglia, yielding hyperresponsive or tolerized states modulating amyloid-β pathology. Convergent mechanisms (H3K4me3, glycolysis, mTOR/AhR/NLRP3) highlight trained immunity as a shared driver of chronic sterile inflammation. Conclusions Trained immunity emerges as a unifying maladaptive mechanism perpetuating low-grade inflammation across these diseases, bridging transient endogenous insults to sustained pathology. Targeting reprogramming pathways, such as glycolysis or epigenetic inhibitors, offers promising therapeutic strategies. Expanded human studies are needed to address preclinical dominance and data gaps, particularly in CKD and neurodegeneration, where evidence is preliminary.
Objective Endothelial progenitor cells (EPCs) originate from hematopoietic stem cells and can be quantified in peripheral blood using flow cytometry. The anti-GM-CSFα antibody (CD116) may serve as a specific marker for EPC enumeration. This study aimed to quantify peripheral EPCs expressing CD116 and compare the results with other specific antibodies in newborns and adults. Materials and Methods EPC enumeration was performed by flow cytometric analysis of peripheral blood leukocytes (PBLs) obtained from 50 individuals, including 25 newborns and 25 adults. A CD34-specific antibody was used to identify hematopoietic stem/progenitor cells, while an antibody panel consisting of CD116, CD146, CD31, and CD45 was employed for EPC identification. Results Enumeration of CD34 + hematopoietic progenitor cells (HPCs) demonstrated that the mean CD34 + HPC count per 10 6 PBLs was 1643 (935–1458) in newborns and 242.7 (163–190) in adults, with a statistically significant difference between the groups ( p < 0.001). Using CD146 staining, the mean number of circulating EPCs per 10 6 PBLs was 94.2 (90.5–129.0) in newborns and 9.2 (7.4–12.4) in adults ( p < 0.001). Similarly, enumeration based on CD31 staining revealed mean EPC counts of 19.0 (12.5–28.0) in newborns and 6.0 (5.0–7.0) in adults ( p < 0.001). Enumeration using CD116 staining showed mean EPC numbers of 29.0 (23.0–34.0) in newborns and 3.0 (2.0–4.0) in adults, also indicating a significant difference between the two groups ( p < 0.001). Conclusion EPC numbers are significantly higher in newborns than in adults, suggesting an important developmental role for these cells. The GM-CSFα-specific antibody (CD116) may serve as a novel auxiliary marker for the identification and quantification of circulating EPCsubpopulations. Furthermore, EPC numbers appear to vary across different life stages, with higher numbers in newborns potentially reflecting the presence of a highly regenerative microenvironment.
IntroductionThe gut microbiota modulates dementia pathogenesis through immune interactions. Using Mendelian randomization, we investigate immune mediated mechanisms linking microbial dysbiosis to four dementia subtypes (Alzheimer's disease, Frontotemporal dementia, Vascular dementia, Parkinson's disease dementia . Our study tests whether gut microbiome effects on dementia are transmitted via immunoregulatory pathways.MethodsGenome wide association studies data included gut microbiota, 731 immune traits, and dementia cohorts (Alzheimer's disease, Frontotemporal dementia, Vascular dementia, Parkinson's disease dementia). Two step Mendelian randomization with Inverse Variance Weighted analyses assessed mediation effects, controlled by F-statistics >10 and Steiger filtering. Sensitivity analyses addressed pleiotropy.ResultsA total of 37 gut microbiome species demonstrated potential causal effects relationships with four types of dementia, and 137 immune cell subsets exhibited potential causal effects associations with these four dementia subtypes. In the Two step Mendelian randomization analysis, CD45RA + CD28- CD8+ T cells, CD19 on IgD- CD38dim B cells, and BAFF-R on CD20- B cells were shown to exert mediating effects between class/order/family.Deltaproteobacteria and Alzheimer's disease. CD4+ CD8+ T cells were found to exert a mediating effect between genus.Roseburia and Parkinson's disease dementia . CD20- CD38- B cells, CD19 on CD20- B cells, and IgD on unswitched memory B cells were found to exert a mediating effect between class/order/family.Coriobacteriales,genus.Lactococcus and Vascular dementia.ConclusionThis Mendelian randomization study revealed that certain immune cells serve as mediators in the pathway by which the gut microbiome contributes to the onset of dementia.
Background Periodontitis is one of the most common inflammatory diseases in humans, mostly caused by bacterial infection and with diverse populations of immune cells involved. Myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells derived from hematopoietic precursor cells, have exhibited immunomodulatory functions by production of different molecules such as inducible NO synthase (iNOS) and it is thought to be involved in periodontitis. However, reports of characterization of cells with MDSC phenotypes in gingival tissues are very scarce. This study aimed to characterize gingival cells with MDSC phenotypes in healthy gingiva and periodontitis tissues.Methods and Results Human healthy gingival tissues and those with periodontitis were included to analyze cells with MDSC phenotypes by flow cytometry. Additionally, a mouse model of experimental periodontitis was used to identify cells with MDSC phenotypes and production of iNOS. Results showed an increased accumulation of CD45+HLA-DRneg/lowCD11b+CD33+ cells in human gingival tissues with periodontitis. Experimental periodontitis promotes accumulation of CD45+CD11b+Gr-1+ and CD45+CD11b+Ly6G+ cells in gingival tissues. Experimental periodontitis did not promote accumulation of these subpopulations in other tissues as spleen. Additionally, gingival CD45+Gr-1+ iNOS+ cells were identified.Conclusions cells with MDSC phenotypes are resident in healthy gingival tissues and their accumulation is locally triggered by periodontitis. Cells with capacity of iNOS production could be implicated in generation of reactive nitrogen species, suggesting immunomodulatory properties.
High-molecular-weight kininogen (HK) is known to bind lipopolysaccharides (LPS) with high affinity and serves as a crucial LPS carrier in circulation, supporting endotoxemia. However, its role in host defense against Gram-negative bacterial infection remains unclear. Here we demonstrate that HK directly binds to Escherichia coli ( E. coli ) via LPS and rapidly localizes to sites of infection. HK-deficient mice ( Kng 1 – /– ) showed increased susceptibility to infection, with increased bacterial dissemination, lung injury, and proinflammatory cytokine production. In contrast, endogenous expression of human HK in Kng 1 – /– mice restored survival, limited bacterial spread, and reduced tissue damage. Mechanistically, HK promoted neutrophil antimicrobial responses by enhancing reactive oxygen species production and microbicidal activity. Consistently, liver-specific HK deficiency recapitulated the impaired bacterial clearance and reduced survival upon E. coli challenge, highlighting the importance of plasma HK. Together, these findings identify HK as a new soluble pattern recognition molecule that senses E. coli invasion and initiates neutrophil-mediated antimicrobial responses, revealing a previously unrecognized protective function of the contact system in innate immunity.
Malaria, a globally prevalent disease caused by Plasmodium species, significantly impacts the immune system, particularly affecting splenic function. This study investigates the therapeutic potential of Indigofera oblongifolia leaf extracts (IOLE) with silver nanoparticles (AgNPs) against Plasmodium chabaudi-induced splenic damage in a female C57BL/6 mice model. Fifty female mice were infected with P. chabaudi and subsequently treated with IOLE AgNPs or chloroquine phosphate. Histopathological and immunohistochemical analyses revealed that IOLE AgNPs effectively restored splenic architecture, reduced inflammatory markers, and improved immune responses compared to the control and chloroquine-treated groups. These findings suggest that IOLE AgNPs may offer a novel therapeutic approach to mitigate splenic dysfunction associated with malaria and provide comparative analysis between established therapies like chloroquine and innovative combination of traditional medical plant and modern nano technology.
Malaria, a globally prevalent disease caused by Plasmodium species, significantly impacts the immune system, particularly affecting splenic function. This study investigates the therapeutic potential of Indigofera oblongifolia leaf extracts (IOLE) with silver nanoparticles (AgNPs) against Plasmodium chabaudi -induced splenic damage in a female C57BL/6 mice model. Fifty female mice were infected with P. chabaudi and subsequently treated with IOLE AgNPs or chloroquine phosphate. Histopathological and immunohistochemical analyses revealed that IOLE AgNPs effectively restored splenic architecture, reduced inflammatory markers, and improved immune responses compared to the control and chloroquine-treated groups. These findings suggest that IOLE AgNPs may offer a novel therapeutic approach to mitigate splenic dysfunction associated with malaria and provide comparative analysis between established therapies like chloroquine and innovative combination of traditional medical plant and modern nano technology.
The gut microbiota plays a crucial role in various physiological functions, such as the production of microbial compounds and maintaining homeostatic equilibrium by complex host-microbial interactions. However, any shift in the constitution and diversity of the microbiota or abnormal interaction with the host can prompt the development of dysbiosis. This review thus illustrates that microbial metabolites, notably short-chain fatty acids, tryptophan metabolites, bile acids, and polyamines, exert significant regulatory effects on innate and adaptive immunological processes, immune response and intestinal barrier integrity through specific receptor activation, involving TLRs, NODs, GPCRs, nuclear receptors, and Wnt/β-catenin. It further explores the disruption of host signalling pathways, caused by dysbiosis, promoting the transcription of specific genes and activating pro-inflammatory pathways. Consequently, this suggests that microbiota acts beyond general health, eventually contributing to gastrointestinal, metabolic, and neurological disorders. Lastly, this review highlights therapeutic approaches required to restore balance and uphold physiological balance.
Background: To determine whether (i) altered levels of acute-phase response (APR)-, inflammation-, and extracellular matrix (ECM)-related proteins in the amniotic fluid (AF) were associated with spontaneous preterm delivery (SPTD) in asymptomatic women with midtrimester short cervix (SCX) and (ii) if SPTD risk severity was related to the expression levels of inflammation-related proteins in the AF. Methods: This retrospective cohort study included 70 singleton pregnant women diagnosed with a SCX (<25 mm) at 17–25 weeks, who were subjected to amniocentesis to exclude intraamniotic inflammation (IAI; defined as AF interleukin [IL]-6 ≥ 2.6 ng/mL). APR ( i.e., h epcidin, kallistatin, MBL, pentraxin-2, RBP4 , and serpin A1) , inflammatory ( i.e., IL-6, IL-8, and resistin) , and ECM-related ( i.e., lumican, MMP-8, TGFBI, and uPA) molecules were assayed in the AF by ELISA. The primary outcome measure was SPTD at <34 weeks. The levels of each identified dysregulated inflammatory mediator were divided into quartiles to assess the correlation between their AF expression profiles and SPTD risk severity. Results: Multivariable Firth logistic regression analyses revealed that elevated AF levels of IL-6, IL-8, kallistatin, pentraxin-2, resistin, and serpin A1, and IAI presence were independently associated with SPTD at <34 weeks after adjusting for baseline covariates. The areas under the curves of the aforementioned mediators ranged from 0.67 to 0.79 for outcome prediction. The odds of SPTD at <34 weeks, even after adjusting for confounders, significantly increased with each increasing quartile of baseline AF levels of IL-6/8, pentraxin-2, and resistin. Conclusions: APR (kallistatin, pentraxin-2, and serpin A1)- and inflammation (IL-6/8 and resistin)-, but not ECM-related mediators in the AF are involved in SPTD development in asymptomatic women with a midtrimester SCX. In particular, SPTD risk (especially risk severity) is associated with the degree of the inflammatory response in the AF, as categorized by inflammatory protein expression profiles, as well as IAI presence.
Bronchial cell pyroptosis and IL-17 respectively contribute- to the pathogenesis of steroid-insensitive asthma. In this study, we aim to explore the relationship between bronchial cell pyroptosis and Th17 in airway inflammation of steroid-insensitive asthma. The steroid-insensitive asthma model of mice was induced by toluene diisocyanate (TDI), which was also intraperitoneally injected with NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inhibitor MCC950. The bronchial epithelial cell pyroptosis was identified in morphology by transmission electron microscope. Protein expressions of pyroptosis cytokines (pro-Caspase-1, Caspase-1 p20, pro-GSDMD, cleaved-GSDMD and HMGB1), IL-17A, IL-17F and phosphorylated STAT3 (p-STAT3) in lung tissues were assessed by western blotting. Th17 in lung tissues was measured by flow cytometry. IL-17A + and p-STAT3 + cells in airway were identified by immunohistochemistry. In steroid-insensitive asthma mice, bronchial epithelial cell pyroptosis was confirmed in morphology using transmission electron microscope. Compared with controls, the protein expressions of Caspase-1 p20, cleaved-GSDMD and HMGB1 in lung tissues were increased in mice with steroid-insensitive asthma, which could be attenuated by MCC950. Th17 cells precentage and proteins expressions of p-STAT3, IL-17A and IL-17F were also increased in lung of steroid-insensitive asthmatic mice, which were also attenuated by MCC950. Similarly, the counts of IL-17A + cell and p-STAT3 + cell were more in airway of steroid-insensitive asthmatic mice than controls, and was attenuated by MCC950. In conclusion, bronchial epithelial cell pyroptosis could promote Th17 inflammation in airway of steroid-insensitive asthma mouse, which will provide further understanding on the interaction between innate immunity and acquired immunity in the pathogenesis of steroid-insensitive asthma.
Mastitis in cattle poses a significant health challenge and results in substantial economic losses for the dairy industry. This study aimed to extend the existing precision-cut bovine udder slices (PCBUS) model as an in vitro model to explore the potential of inducing trained immunity in the udder with the goal to use the resulting knowledge for potential new treatment strategies. Interestingly, incubation of PCBUS with 10% fetal calf serum (FCS), but no 2% or FCS-free, negatively affected the production of some of the chemokines/cytokines analysed. When trained immunity was induced by zymosan, followed by stimulation with E. coli -derived lipopolysaccharide (LPS), production of interleukin (IL)-1β, IL-6, tumor necrosis factor α and interferon (IFNγ) was downregulated while production of IL-17A and pro-resolving lipid mediators (leukotrienes and prostaglandins) was upregulated. While the current experimental setup did not definitively confirm the induction of trained immunity for all parameters analysed in PCBUS, it validated the utility of PCBUS as a robust in vitro model for studying bovine udder inflammation. This model offers a promising platform for developing innovative mastitis treatments, particularly given the growing concern over antimicrobial resistance, as well as offering alternatives to the use of live animals in experimental studies in line with the 3Rs principles. It also provides a valuable tool for advancing our understanding of immune responses in the bovine udder. By adapting the precision-cut tissue slice technique to bovine udders, this model enables extensive research into new therapeutic approaches and supports basic research efforts to characterise complex pathophysiological processes associated with mastitis. Furthermore, our data highlight the potential limitations of FCS in in vitro studies. Our data should not only stimulate the discussion about FCS in homologues or heterologues species, but should also be kept in mind regarding the need for foetal calves to generate FCS in line with the 3Rs guideline.
The type I interferon family of cytokines are rapidly produced following innate pattern recognition receptor engagement and establish a critical early state of host defense. Type I interferons act in antiviral immunity as transcriptional activators and the binding of any type I interferon to the common IFNAR receptor triggers the transcription of I nterferon S timulated G enes (ISGs). A defined set of ISGs have been described through exhaustive studies and the protein products of these ISGs function to increase cell intrinsic resistance to viral growth and to promote viral clearance. Simultaneously, interferons also drive a much less well studied program of transcriptional suppression, inhibiting the expression of an unknown number of genes, with poorly understood consequences for disease. The limited number of genes currently known to be transcriptionally suppressed by IFN are enriched for those with immune-mediating activities such as inflammatory cytokines (e.g., IL-1β), cytokine receptors (e.g., IFNγR) and chemokines. Interferon dependent transcriptional suppression of immune response genes is therefore thought to underlie the immune suppression associated with interferon production during many bacterial infections (e.g., mycobacterium tuberculosis and listeria monocytogenes) and may also explain the palliative effects of interferons in some autoimmune diseases. Despite the health relevance of IFN driven transcriptional suppression, no consensus molecular model exists to explain its selectivity or regulation. In this review we highlight the current literature detailing the known targets of IFN transcriptional suppression within the various disease models in which it has been observed. We also review the relevant molecular mechanisms which have been proposed to explain transcriptional suppression by interferons and discuss the remaining open questions in this field with an ambition to stimulate future work in this area.
Neutrophils play a pivotal role in the host immune system, serving as the frontline defense against microbial infections. They eradicate pathogens through diverse mechanisms, encompassing degranulation, phagocytosis, and the release of reactive oxygen species. Moreover, they are acknowledged as crucial contributors to chronic inflammatory pathological processes, including conditions such as cancer and autoimmune diseases. An expanding body of research suggests that neutrophils, harnessing their innate immune characteristics, possess the potential to serve as carriers for therapeutic agents or be directly employed in disease treatment. This underscores their potential as a cell therapy platform for future applications. Consequently, we systematically investigate the potential applications of neutrophils in this review, with a primary emphasis on elucidating the research advancements in utilizing neutrophils, including those derived from stem cells, for therapeutic interventions in various diseases.
The gut microbiome plays a crucial role in shaping immune responses, and its connection to immunity has never been more relevant than in the COVID-19 era. The interaction between gut microbes and the immune system, known as microbiome-immunity crosstalk, influences both how the body responds to infections and how well it recovers. COVID-19, whether in its acute phase or lingering as long COVID, has been linked to disturbances in the gut microbiome. During infection, many patients experience dysbiosis—an imbalance in gut bacteria—that can contribute to immune dysfunction and excessive inflammation. This imbalance may not only worsen the severity of the disease but also prolong recovery, leading to persistent symptoms like fatigue, brain fog, and digestive issues. Long COVID, in particular, has been associated with ongoing immune dysregulation, where the body's defense system remains in a state of heightened activation, causing chronic inflammation. Given the strong link between gut health and immunity, there is growing interest in strategies to restore microbial balance. Synbiotics—combinations of probiotics (beneficial bacteria) and prebiotics (nutrients that support them)—are being explored as a potential therapeutic approach. By replenishing beneficial gut microbes, synbiotics may help regulate immune responses, reduce inflammation, and support overall recovery from COVID-19. Emerging research suggests that improving gut health could enhance the body's ability to fight infections and recover more efficiently. As we continue to understand the long-term impact of COVID-19, focusing on the gut microbiome offers a promising path forward. Supporting a balanced and diverse microbiome through diet, lifestyle, and targeted interventions like synbiotics may provide a natural way to strengthen immunity and improve health outcomes in both acute and long COVID cases.
Extracellular vesicles (EVs), which are nanosized membranous structures released by diverse cell types, serve as crucial mediators of intercellular communication. Recent evidence has highlighted the dynamic transfer of various biological components, including proteins, lipids, mRNAs, non-coding RNAs, miRNAs, and DNA, via EVs. Immuno-stimulated cells actively release EVs that play a pivotal role in regulating the innate immune system. This study comprehensively reviews the current scientific findings, shedding light on the intricate biological roles of EVs in regulating innate immune cells and the overall immune system. This discussion encompasses diverse pathophysiological conditions and provides valuable insights into the multifaceted contributions of EVs to innate immune responses.
ObjectiveTo research whether radiation-induced liver damage and fibrosis could be mitigated by resveratrol (RSV) and to elucidate its underlying mechanism.MethodsA radiation-induced liver damage (RILD) model of murine was constructed. RSV was used as an intervention agent. The effects of RSV on inflammatory reaction, apoptosis, senescence, fibrosis, survival, and liver functions were detected by β-Gal, Sirius red, Masson's trichrome, and Tunnel staining using an automated biochemistry analyzer. The protein expression levels of P16 and P21 were detected by Western blot.ResultsRSV alleviated inflammatory injury of RILD mice. RSV decreased the serum pro-inflammatory cytokines of RILD mice. RSV alleviated radiation-induced hepatocellular senescence. The protein expression levels of P16 and P21 in RILD mice were decreased with RSV administration. RSV decreased the number of apoptotic cells in the early stage of RILD. RSV alleviated liver fibrosis and liver function in RILD mice.ConclusionsRSV reduces RILD and fibrosis, and may be related to inhibiting cellular aging and reducing inflammation.
