Molecular Immunology[JOURNAL]
Sun
200 papers
DAP12 affects the acute inflammatory response caused by UPEC or LPS by regulating macrophage infiltration.
Sun S, Yi R, Wang X … +8 more , Zhang Y, Liu M, Wang L, Niu Z, Jia R, Dong Z, Xiong H, Wang C
Mol Immunol · 2025 Oct · PMID 40834506 · Publisher ↗
Urinary tract infection (UTI) is a prevalent bacterial infection, predominantly caused by uropathogenic Escherichia coli (UPEC). Severe UTIs can lead to kidney damage, which is closely associated with increased infiltrat...
Urinary tract infection (UTI) is a prevalent bacterial infection, predominantly caused by uropathogenic Escherichia coli (UPEC). Severe UTIs can lead to kidney damage, which is closely associated with increased infiltration of M1-type macrophages. DNAX-activating protein of 12 kD (DAP12) is extensively expressed in myeloid cells and natural killer (NK) cells, and it can interact with TREM receptors to mediate various immune responses. Our study revealed that DAP12 deletion significantly mitigated kidney injury induced by UPEC infection, a phenomenon strongly correlated with reduced macrophage infiltration. Further investigation demonstrated that DAP12 directly regulates the polarization of macrophages during UPEC infection. In an endotoxin shock model induced by LPS derived from E. coli, DAP12 deficiency similarly decreased mortality and inhibited LPS-induced macrophage polarization in mice. Collectively, these findings suggest that the TREM1-DAP12 signaling pathway plays a critical role in kidney injury caused by UPEC infection, indicating that this pathway could serve as a novel therapeutic target for treating UPEC-induced kidney damage.
Formononetin ameliorates allergic asthma by inhibiting JUN and suppressing type Ⅱ immune responses mediated by ILC2 cells.
Liu J, Li Y, Liu M … +3 more , Li X, Liu C, Zhu Y
Mol Immunol · 2025 Oct · PMID 40834505 · Publisher ↗
OBJECTIVE: Formononetin (FM), a flavonoid with potent anti-inflammatory effect, was investigated for its therapeutic potential and underlying mechanisms in allergic asthma (AS). METHODS: An ovalbumin (OVA)-induced murine...
OBJECTIVE: Formononetin (FM), a flavonoid with potent anti-inflammatory effect, was investigated for its therapeutic potential and underlying mechanisms in allergic asthma (AS). METHODS: An ovalbumin (OVA)-induced murine model of AS was established and treated with FM. Inflammatory responses, mucus secretion, and the activation and migration of type II innate lymphoid cells (ILC2s) were assessed using histological staining, ELISA, flow cytometry, and molecular analysis. The role of the JUN gene was further explored using the JUN agonist 15(S)-HpETE. In vitro assays were conducted to evaluate FM's effects on ILC2 proliferation and cytokine expression. RESULTS: FM significantly alleviated airway inflammation, reduced mucus hypersecretion, and lowered serum IgE levels. It decreased the abundance and activation of ILC2s in lung tissues and suppressed the expression of related cytokines and transcription factors. Notably, FM inhibited the lung-gut axis migration of ILC2s by reducing iILC2 and nILC2 levels in the small intestine and iILC2 levels in the lung. In vitro, FM suppressed ILC2 proliferation and activation. These effects were reversed by 15(S)-HpETE, suggesting a JUN-dependent mechanism. CONCLUSIONS: FM ameliorates AS by inhibiting type II immune responses and ILC2 migration via targeting JUN. These findings suggest FM as a promising candidate for asthma therapy.
ALKBH5-mediated mA demethylation modification of RAD51 inhibits osteogenic differentiation via promoting DNA damage in osteoporosis.
Qiu M, Liao Z, Wu X … +4 more , He P, Wen X, Xie Y, Qi J
Mol Immunol · 2025 Oct · PMID 40819549 · Publisher ↗
Osteoporosis (OP) is a metabolic disorder characterized by reduced bone mineral density and degeneration of bone tissue microarchitecture. Osteogenic differentiation plays a pivotal role in OP pathogenesis by facilitatin...
Osteoporosis (OP) is a metabolic disorder characterized by reduced bone mineral density and degeneration of bone tissue microarchitecture. Osteogenic differentiation plays a pivotal role in OP pathogenesis by facilitating new bone formation, preserving bone strength and density, and counteracting bone resorption. RNA epigenetic modifications have been increasingly implicated in multiple aspects of bone metabolism. Our previous studies revealed the regulatory role of RAD51 in OP progression. This study aimed to investigate whether RAD51 undergoes RNA methylation modification to participate in OP and to elucidate its underlying mechanisms. MC3T3-E1 cells were induced to undergo osteogenic differentiation and exposed to a simulated microgravity environment to establish an in vitro OP model. An ovariectomized (OVX) murine OP model was also established. RNA methylation level was quantified using dot blot assay. RT-qPCR was employed to analyze mRNA expression of mA methyltransferases and demethylases. Osteogenic differentiation capacity was assessed by Alizarin Red S and alkaline phosphatase (ALP) staining. Protein expressions were evaluated by Western blot. The interaction between RAD51 and AlkB Homolog 5 (ALKBH5)/YTH domain family (YTHDF)1 was validated through RNA immunoprecipitation and dual-luciferase reporter assays. Results demonstrated that ALKBH5-mediated mA demethylation significantly suppressed RAD51 expression in MC3T3-E1 cells. Furthermore, ALKBH5 knockdown enhanced osteoblast differentiation by alleviating DNA damage. Mechanistically, the ALKBH5/YTHDF1 mA regulatory axis modulated RAD51 mRNA stability through mA methylation dynamics. In vivo experiments revealed that ALKBH5 deletion mitigated bone loss and promoted osteoblastogenesis in OVX mice through inhibition of DNA damage pathways. Collectively, these findings indicated that ALKBH5-mediated mA demethylation of RAD51 inhibited osteogenic differentiation by inducing DNA damage in OP, suggesting potential therapeutic targets for osteoporosis treatment.
Expression of immunogenic cell death-related genes is correlated with the immune microenvironment and predicts prognosis in lung adenocarcinoma.
Gao F, Liang Y, Gong W
Mol Immunol · 2025 Oct · PMID 40819548 · Publisher ↗
Immunogenic cell death (ICD) is a type of regulated cell death that is sufficient to prime adaptive immune responses. Mounting evidence has demonstrated that ICD has the potential to modify the tumor immune microenvironm...
Immunogenic cell death (ICD) is a type of regulated cell death that is sufficient to prime adaptive immune responses. Mounting evidence has demonstrated that ICD has the potential to modify the tumor immune microenvironment through the release of numerous damage-associated molecular patterns (DAMPs), which may contribute to the effects of immunotherapy. We aimed to explore the expression profile of ICD-associated biomarkers in lung adenocarcinoma (LUAD) and construct a prognostic signature based on these genes. In this study, we identified two ICD-associated molecular subgroups with significantly different survival rates. Cluster 1 was associated with a favorable prognosis and a high abundance of immune-infiltrating cells and a relatively high immune status. Functional analyses revealed that the differentially expressed genes (DEGs) between the two subgroups were mainly involved in immune response signaling. In addition, a risk score signature established based on 11 ICD-related genes showed notable potential for predicting the prognosis of patients with LUAD. Analysis of immune profiles indicated that the low-risk group had noticeable immune cell infiltration and was more likely to benefit from immunotherapy. In conclusion, we established a new classification system for LUAD based on the ICD signature. This stratification can notably guide clinical practice for assessment of patient prognosis as well as potential immunotherapy for patients with LUAD.
Effects of long-distance transport on glycolipid metabolism and immune function in simmental calves.
Xu C, Zhou Y, Ye Z … +6 more , Ni Y, Han X, Liu Y, Sun Z, Liu H, Chen Y
Mol Immunol · 2025 Oct · PMID 40818166 · Publisher ↗
This study seeks to examine the effects of long-distance transportation on Simmental calves. While it is established that long-distance transportation can influence animal health, the specific impacts on glucose and lipi...
This study seeks to examine the effects of long-distance transportation on Simmental calves. While it is established that long-distance transportation can influence animal health, the specific impacts on glucose and lipid metabolism, as well as immune function in cattle, remain inadequately understood. This study analyzed blood samples from twelve 5-month-old Simmental calves that were transported over a distance of 1100 km from Tongliao City, Inner Mongolia, to Zouping City, Shandong Province, with a transportation duration of 15 h. The investigation focused on comparing alterations in serum glucose metabolism, lipid metabolism, and immune parameters before and after the transportation process. The findings indicated that, in contrast to pre-transportation levels, there was an upregulation of enzymes associated with glycolysis and the pentose phosphate pathway post-transportation, resulting in enhanced glucose utilization. Additionally, levels of creatine kinase and lactate dehydrogenase were found to be elevated. The activities of fatty acid synthase and acetyl-CoA carboxylase also increased, while total cholesterol and triglyceride levels decreased, accompanied by a rise in non-esterified fatty acids. Furthermore, high-density lipoprotein cholesterol levels increased, whereas low-density lipoprotein cholesterol levels decreased. Cortisol levels exhibited an upward trend, and there was a significant increase in pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, as well as immunoglobulin G. In conclusion, long-distance transportation appears to induce disorders in glucose and lipid metabolism, systemic inflammation, and immune dysfunction in Simmental calves.
Gelatin enhances bacteria-phagocytosis via a ROS-mitochondria-STING axis in differentiated human macrophage-like U937 cells.
Sun X, Li M, Ma Y … +9 more , Chen K, Jiang S, Hayashi T, Itoh K, Mizuno K, Hattori S, Fujisaki H, Liu W, Ikejima T
Mol Immunol · 2025 Oct · PMID 40815890 · Publisher ↗
The recruitment of macrophages to a pathological site is accompanied by the change in surrounding extracellular matrix. The pathological foci in a highly inflammatory status contain certain amounts of gelatin, the denatu...
The recruitment of macrophages to a pathological site is accompanied by the change in surrounding extracellular matrix. The pathological foci in a highly inflammatory status contain certain amounts of gelatin, the denatured form of collagen. We previously revealed that precoating the cell dishes with gelatin, but not type I collagen, enhances bacteria-phagocytosis capacity of phorbol 12-myristate 13-acetate (PMA)-treated macrophage-like human histiocytic lymphoma U937 cells. The present study further reveals that gelatin-precoating increases the amount of reactive oxygen species (ROS) in PMA-treated U937 cells, which contributes to the enhanced phagocytosis of bacteria, including both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. ROS in cells on gelatin-precoated culture plates cause impairments on mitochondria, as shown by the reduced mitochondrial membrane potential and ATP levels, as well as the increase in oxidative lesions in mitochondrial DNA. These mitochondrial damages lead to the activation of stimulator of interferon genes (STING) pathway, which enhances the bacteria-phagocytosis in PMA-treated U937 cells. Simultaneously, mitophagy-related proteins, such as PINK1, parkin and LC3 II, all increase following the elevation of ROS levels. Of note, mitophagy restricts the mitochondrial disorders, forming a feedback negative regulation for the effects of ROS, and works against bacteria-phagocytosis. This study reveals a core function of ROS-mitochondria-STING axis during gelatin-enhanced bacteria-phagocytosis in PMA-stimulated macrophage-like U937 cells, and provides possibility for clinically applying gelatin as a protectant for bacterial infection in some lesions.
Bta-miR-25 alleviates lipopolysaccharide-induced endometritis in cows by targeting DUSP10 to inhibit MAPK signaling.
Zhang Z, Wang X, Shi QT … +5 more , Lu LG, Yan XZ, Qi X, Zhang ZJ, Wang EY
Mol Immunol · 2025 Oct · PMID 40815889 · Publisher ↗
Bovine endometritis is a common and serious disease that has caused huge economic losses and a decline in production performance in the dairy cattle industry. This study aimed to investigate the regulatory role of bta-mi...
Bovine endometritis is a common and serious disease that has caused huge economic losses and a decline in production performance in the dairy cattle industry. This study aimed to investigate the regulatory role of bta-miR-25 in Lipopolysaccharide (LPS)-induced BEND and its impact on endometritis. In this study, an in vitro endometritis model was constructed using LPS. The expression levels of proinflammatory cytokines IL-6, IL-8, IL-1β, and TNF-α were significantly increased in the model, while the expression of bta-miR-25 was upregulated, and its target gene DUSP10 was downregulated. We further validated DUSP10 as a target gene of bta-miR-25 through a dual-luciferase reporter gene assay. Knockdown of bta-miR-25 can increase the decreased expression of DUSP10 levels and inhibited the increase in inflammatory factors induced by LPS. Subsequently, overexpression DUSP10 also inhibited the LPS-induced increase in inflammatory factors. In summary, bta-miR-25 can inhibit LPS-induced endometritis by over the expression of DUSP10. bta-miR-25 and DUSP10 may serve as biomarkers and potential therapeutic targets for endometritis in dairy cows.
YY1/INSIG1 enhances atherosclerosis progression by regulating AMPK-mTOR signaling.
Yang M, Zhang J, Xu Z … +2 more , Yang L, Tang S
Mol Immunol · 2025 Oct · PMID 40815888 · Publisher ↗
OBJECTIVE: The regulatory mechanisms of Insulin-Induced Gene 1 (INSIG1) in atherosclerosis (AS) remain largely unknown. This study aimed to investigate the role of the YY1/INSIG1 axis and its regulation of the AMPK-mTOR...
OBJECTIVE: The regulatory mechanisms of Insulin-Induced Gene 1 (INSIG1) in atherosclerosis (AS) remain largely unknown. This study aimed to investigate the role of the YY1/INSIG1 axis and its regulation of the AMPK-mTOR signaling pathway in AS pathogenesis. METHODS: Atherosclerosis mouse models were established. RNA sequencing was performed to determine differentially expressed genes. Human umbilical vein endothelial cells (HUVECs) and human vascular smooth muscle cells (HVSMCs) were treated with ox-LDL and/or transfected with plasmids for INSIG1. Cellular functions were evaluated by proliferation, migration, and inflammation assays. Key proteins in the AMPK/mTOR pathway were measured by western blotting. The regulation of INSIG1 by transcription factor YY1 was confirmed using a dual-luciferase reporter assay. Crucially, the functional role of the INSIG1-AMPK axis was validated in vivo using an AMPK inhibitor (Dorsomorphin, DM) in the AS mouse model. RESULTS: INSIG1 expression was significantly downregulated in atherosclerosis mouse models and patients. In HUVECs, INSIG1 promoted cell proliferation, migration, and invasion, while in HVSMCs, INSIG1 suppressed these functions. Higher INSIG1 levels reduced the proinflammatory mediators IL-6 and MCP-1. INSIG1 overexpression activated AMPK and inhibited mTOR phosphorylation. Crucially, in the mouse model, the protective anti-atherosclerotic effects of INSIG1 overexpression were significantly abolished by the administration of the AMPK inhibitor DM. Bioinformatics suggested a potential interaction between YY1 and INSIG1 in atherosclerosis, which was confirmed by a dual-luciferase reporter assay that demonstrated YY1 directly regulate the mRNA transcription of INSIG1. CONCLUSION: These findings underscore the relevance of INSIG1 and YY1 in atherosclerosis and maybe in its treatment.
PCBP2 alleviates myocardial infarction by inhibiting cardiomyocyte ferroptosis via the NDUFS1/NRF2 pathway.
Zhang Q, Jin A, Cheng H … +2 more , Zheng Y, Li B
Mol Immunol · 2025 Oct · PMID 40784311 · Publisher ↗
BACKGROUND: Poly(C) binding protein 2 (PCBP2) was reported to alleviate cardiomyocyte damage, but its molecular mechanism remains unclear. The current study aimed to investigate the role and potential mechanism of PCBP2...
BACKGROUND: Poly(C) binding protein 2 (PCBP2) was reported to alleviate cardiomyocyte damage, but its molecular mechanism remains unclear. The current study aimed to investigate the role and potential mechanism of PCBP2 in progression of MI. METHODS: An in vivo MI model was established by ligation of the left anterior descending (LAD) branch in mice. PCBP2 expression was detected in Normal and MI groups. H9C2 cells were treated with OGD for 0, 2, 4, and 6 h to screen for optimal time to establish MI model in vitro. H9C2 cells were transfected with pcDNA-PCBP2, and the effect of PCBP2 overexpression on OGD-induced oxidative stress, inflammation and ferroptosis was evaluated. Subsequently, the interaction of PCBP2 with NDUFS1 mRNA was predicted by the Starbase database and verified by RNA-immunoprecipitation (RIP) and RNA-protein pull-down assay. Next, a series of reversal experiments were performed to verify the regulation of PCBP2 on NDUFS1 expression. Then, pcDNA-NDUFS1 was transfected into H9C2 and MIND4-17 (NRF2 protein activator) treated for reversal experiments to assess the effect of NDUFS1 on NRF2-mediated ferroptosis. Finally, LV-PCBP2 and LV-NDUFS1 lentiviral vectors were intrapericardially injected into MI mice, and the role of PCBP2 and NDUFS1 in the progression of MI was verified in vivo. RESULTS: PCBP2 was downregulated in MI model and OGD-induced H9C2 cells. PCBP2 improved cell proliferation and inhibited oxidative stress, inflammation and ferroptosis in OGD-incubated H9C2 cells. PCBP2 bound with NDUFS1 mRNA and promoted NDUFS1 expression in H9C2 cells, which promoted NRF2 activation by enhancing NRF2 nuclear translocation and inhibited NRF2-mediated ferroptosis. Finally, administration of LV-PCBP2 and LV-NDUFS1 alleviated myocardial tissue injury and MI infarct in mice through suppressing cardiomyocyte ferroptosis and inflammation. CONCLUSION: Our results suggested that PCBP2 alleviated MI by inhibiting cardiomyocyte ferroptosis through interacting with NDUFS1 mRNA and activating NRF2-Keap1 pathway.
Luteolin attenuates type 2 inflammation in asthmatic mice induced by OVA by regulating IL-33/ST2- GSK3β-M2 macrophage polarization.
Huang X, Yu H, Zhou Y … +9 more , Xie C, Shi H, Chen M, Tang W, Chen W, Song J, Gao Z, Dong J, Luo Q
Mol Immunol · 2025 Oct · PMID 40752323 · Publisher ↗
Allergic asthma is a prevalent non-infectious inflammatory disease characterized by type 2 inflammation. Although multiple treatment options are available, their efficacy is often limited due to the heterogeneous nature...
Allergic asthma is a prevalent non-infectious inflammatory disease characterized by type 2 inflammation. Although multiple treatment options are available, their efficacy is often limited due to the heterogeneous nature of asthma. Luteolin (LUT), a naturally occurring flavonoid, has demonstrated therapeutic potential in various inflammatory conditions. The aim of this research is to investigate the underlying pathogenesis mechanisms of allergic asthma and to evaluate the therapeutic effects of LUT on allergic asthma via IL-33/ST2 signaling pathway. We established a murine model of allergic asthma by sensitizing and challenging BALB/c mice with ovalbumin (OVA), followed by treatment with LUT. The effects of LUT in allergic asthma mice were evaluated via the following techniques: pathological staining, Immunohistochemical staining (IHC), enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). Additionally, we also used IL-33 to stimulate RAW264.7 cells. Assays in vitro including cell counting Kit-8 (CCK-8), RT-qPCR and WB were performed to investigate potential mechanisms of LUT on IL-33/ST2 pathway activation and M2 macrophages polarization. LUT was verified to have crucial effects on ameliorating asthmatic mice lung function as evidenced by down-regulated airway resistance by 23 % and 48 % (p < 0.05 vs. OVA/saline group); regulating airway type 2 inflammation via decrease the content of type 2 inflammatory cytokines (IL-4, IL-5, and IL-13) by 17 %-78 % (**p < 0.01; p < 0.001 vs. OVA/saline group); decreasing airway inflammatory cells infiltration by 54 % and 65 % (p < 0.001 vs. OVA/saline group); inhibiting mucus secretion by 75 % and 89 % (p < 0.001 vs. OVA/saline group). Mechanistic research revealed that LUT can treat asthma via IL-33/ST2-GSK3β-M2 macrophages polarization pathway, thereby regulating airway inflammation, remodeling, and immune responses in allergic asthma. Collectively, these findings support LUT as a promising therapeutic agent for allergic asthma through targeted modulation of the IL-33/ST2-GSK3β-M2 macrophage polarization axis.
The role of microglia in neurodegenerative diseases.
Nie DA, Yu J, Huang W … +3 more , Li GH, He XY, Xu JH
Mol Immunol · 2025 Sep · PMID 40749622 · Publisher ↗
As resident immune surveillance cells within the central nervous system (CNS), microglia exert pivotal biological functions in maintaining CNS homeostasis through dynamic modulation of their proliferative capacity, chemo...
As resident immune surveillance cells within the central nervous system (CNS), microglia exert pivotal biological functions in maintaining CNS homeostasis through dynamic modulation of their proliferative capacity, chemotactic motility, efferocytosis activity, and biphasic secretory mechanisms involving both neuromodulatory factors and pro-inflammatory mediators. These specialized macrophages not only serve as the first line of defense in innate immunity but also orchestrate the regulation of adaptive immune responses; whose functional status directly governs both the physiological integrity of neural circuits and the progression of pathological outcomes. Notably, in neurodegenerative disease models, microglial functional states exhibit pronounced heterogeneity and are tightly regulated by microenvironmental cues. Upon encountering sustained hyperactivation or functional impairment, these cells precipitate a cascade of deleterious events within the neurovascular unit. Building upon these pathophysiological mechanisms, targeted modulation of microglial polarization equilibrium has emerged as a pivotal research focus in developing innovative neuroprotective therapeutic strategies. This review systematically integrates empirical evidence derived from cutting-edge methodologies-including molecular imaging, single-cell multi-omics profiling, and conditional genetic ablation-to mechanistically dissect the dual regulatory roles of microglia in orchestrating neural homeostatic maintenance and driving pathological progression in neurological disorders.
Choline reduces inflammatory response and lipid accumulation in calf hepatocytes induced by NEFA via inhibiting ROS/ NF-κB/NLRP3 inflammasome axis.
Zhang R, Du X, Hu H … +7 more , Chen J, Yu J, Wang L, Yao J, Liu S, Wang J, Cao Y
Mol Immunol · 2025 Sep · PMID 40743943 · Publisher ↗
Perinatal dairy cows are highly susceptible to fatty liver syndrome, a prevalent metabolic disorder characterized by excessive hepatic lipid accumulation. Although inflammatory progression drives the transition from phys...
Perinatal dairy cows are highly susceptible to fatty liver syndrome, a prevalent metabolic disorder characterized by excessive hepatic lipid accumulation. Although inflammatory progression drives the transition from physiological lipid storage to pathological steatosis, the underlying mechanisms remain incompletely understood. This study investigates the therapeutic potential of choline in non-esterified fatty acid (NEFA)-induced hepatic inflammation and lipid metabolism dysregulation using an in vitro calf hepatocytes model. A hepatic steatosis model was established by treating primary calf hepatocytes with 1.2 mM NEFA for 24 h. Choline supplementation (75 μM) significantly enhanced hepatocyte viability and reduced intracellular triglyceride (TG) content (P < 0.05). Transcriptomic analysis demonstrated that choline downregulated key components of the NLRP3 inflammasome (P < 0.05) and interleukin-1β (IL-1β) expression (P < 0.05). Mechanistically, choline attenuated NF-κB phosphorylation (P < 0.05) and suppressed intracellular reactive oxygen species (ROS) generation (P < 0.05), thereby inhibiting NLRP3 inflammasome assembly and subsequent IL-1β maturation (P < 0.05). Notably, activation of NLRP3 inflammasome complete abolished choline's protective effects on lipid homeostasis and inflammatory responses (P < 0.05). These findings demonstrate that choline ameliorates NEFA-induced hepatic steatosis by modulating the ROS/NF-κB-NLRP3-IL-1β/IL-18 signalling axis, providing novel therapeutic targets for intervention of steatohepatitis in periparturient dairy cows.
miR-146a-5p targets IRAK1/TRAF6 to promote bacillus Calmette-Guérin survival by exosome-mediated autocrine actions.
Chen HR, Huang HS, Zeng SY … +8 more , Sun YF, Chen L, Lai SY, Wang JJ, Yang F, Pi J, Cong YG, Xu JF
Mol Immunol · 2025 Sep · PMID 40730095 · Publisher ↗
BACKGROUND: Exosomes carry signaling molecules between cells and play important roles in the interaction between macrophages and Mycobacterium tuberculosis (Mtb). This study aimed to examine the function and content of e...
BACKGROUND: Exosomes carry signaling molecules between cells and play important roles in the interaction between macrophages and Mycobacterium tuberculosis (Mtb). This study aimed to examine the function and content of exosomes secreted by macrophages infected with Bacillus Calmette-Guérin (BCG). METHODS: THP-1 monocytes and HEK293T cells were used. Macrophages were infected with BCG. A Transwell system was used to evaluate the effect of the exosomes secreted by macrophages. Cells were transfected with the miR-146a-5p plasmid or inhibitor to examine the effects of miR-146a-5p overexpression or inhibition. qRT-PCR was employed to investigate the expression levels of miR-320a-5p, miR-27a-5p, miR-26a-5p, miR-146a-5p, and miR-223-5p and the mRNA expression of IL-6, TNF-α, and IL-1β. Western blot was used to investigate the protein expression of IRAK1, TRAF6, CD63, CD81, GRP94, Alix, TSG101, P65, and p-P65. A dual luciferase assay was performed to investigate whether miR-146a-5p targets IRAK1 and TRAF6. RESULTS: The infected cells contained high miR-146a-5p levels that could be secreted into exosomes. Exosomal miR-146a-5p promoted Mtb survival and proliferation after uptake by host cells. Bioinformatics showed that high miR-146a-5p levels were found in exosomes from BCG-infected macrophages and blood samples from patients with tuberculosis. The phagocytosis of exosomes containing miR-146a-5p by BCG-infected macrophages suppressed the expression of inflammatory factors by regulating the IRAK1-TRAF6-NF-κB signaling pathway, ultimately leading to the inhibition of inflammatory factor expression in macrophages and a decrease in the macrophage BCG killing capacity. CONCLUSION: The findings indicate a new immune evasion mechanism of Mtb. miR-146a-5p secreted in exosomes by BCG-infected macrophages can decrease the bactericidal potential of macrophages. The results offer a novel theoretical basis and potential biomarkers for diagnosing, treating, and managing tuberculosis.
Regulation of macrophage pyroptosis by SIRT1 during Pseudomonas aeruginosa-induced pneumonia.
Ding H, Xiao X, Zhan Y … +3 more , Lin Y, Xu C, Zeng Y
Mol Immunol · 2025 Sep · PMID 40714269 · Publisher ↗
Pseudomonas aeruginosa (PA), an opportunistic gram-negative bacterial pathogen, is the main cause of lung infections. Pulmonary infection induced by PA results in inflammatory lung injury characterized by macrophage pyro...
Pseudomonas aeruginosa (PA), an opportunistic gram-negative bacterial pathogen, is the main cause of lung infections. Pulmonary infection induced by PA results in inflammatory lung injury characterized by macrophage pyroptosis. In our study, a mouse model of pulmonary infection was established by tracheal intubation with PA in vivo, and the MH-S macrophage line was stimulated with PA in vitro. HE staining was performed to observe changes in the lung tissue. The mechanism was further explored through various methods, including flow cytometry, LDH release assays, ELISA, real-time PCR, Western blotting (WB), and CCK8 assays. Additionally, the effect of MH-S cells on the proliferation of alveolar endothelial cells was observed by coculturing these two cell types. The results showed that PA-induced inflammatory injury in murine lung tissues increased the levels of inflammatory factors (IL-1β/6/12) and pyroptosis-related proteins (NLRP3, Caspase 1/11, and GSDMD-N) and promoted pulmonary macrophage pyroptosis. PA downregulated Sirt1 expression and increased p-NF-κB-p65 levels both in vitro and in vivo. Sirt1 activation or overexpression alleviated PA-induced lung tissue injury, inhibited macrophage pyroptosis, and decreased the expression of inflammatory factors and pyroptosis-related proteins. Sirt1 inhibition or knockdown critically strengthened the effect of PA on pulmonary macrophage pyroptosis. NF-κB inhibition suppressed the PA-induced increase in Sirt1-regulated pyroptosis in MH-S macrophages, decreased the levels of inflammatory factors and pyroptosis-related proteins, and weakened the inhibitory effect of MLE-12 cell proliferation on PA-infected MH-S cells. In conclusion, the Sirt1/NF-κB axis negatively regulates PA-induced inflammatory factor release and macrophage pyroptosis, promotes lung epithelial cell proliferation, and reduces inflammatory injury to the lung tissue.
Leven PRO-CR mediates 5-HT and gut microbiota via TPH1 to improve slow-transit constipation.
Xia F, He Q, Wang S … +3 more , He M, Fang P, Yu Y
Mol Immunol · 2025 Sep · PMID 40712318 · Publisher ↗
Slow-transit constipation (STC) is a chronic disorder causing prolonged colonic transit and discomfort; this study explores the therapeutic potential of probiotics mixture (Leven PRO-CR) in modulating gut microbiota and...
Slow-transit constipation (STC) is a chronic disorder causing prolonged colonic transit and discomfort; this study explores the therapeutic potential of probiotics mixture (Leven PRO-CR) in modulating gut microbiota and enhancing intestinal motility. A loperamide-induced STC mouse model was established, and the effects of Leven PRO-CR treatment were evaluated by measuring defecation frequency, stool water content, and intestinal transit rate. Histopathological analyses, including Hematoxylin & Eosin (H&E) staining, immunohistochemistry (IHC), and TUNEL assay, were performed to assess colonic tissue integrity, interstitial cells of Cajal (ICCs) density, and apoptosis. The expression levels of serotonin (5-HT)-related markers (TPH1, 5-HT receptors, SERT) and enteric neural markers (NOS1, BDNF, TRPV1, GDNF) were analyzed using quantitative PCR (qPCR), Western blotting, and immunofluorescence staining. The gut microbiota composition was examined through 16S rDNA sequencing. Statistical analyses were conducted using GraphPad Prism, with significance set at P < 0.05. Leven PRO-CR significantly improved STC symptoms by reducing first defecation time, increasing stool frequency, fecal water content, and intestinal transit rate. We found that Leven PRO-CR restored colonic tissue integrity, enhanced ICC survival by upregulating c-Kit/SCF signaling, and reduced apoptosis. Leven PRO-CR upregulated TPH1 expression, increased 5-HT levels, and inhibited its degradation, thereby promoting intestinal motility. Leven PRO-CR also modulated NOS1, BDNF, TRPV1, and GDNF mRNA and protein expression, suggesting enhanced enteric nervous system function. 16S rDNA sequencing revealed increased microbial diversity and a restored balance of beneficial bacteria after Leven PRO-CR treatment, indicating the beneficial effects of Leven PRO-CR on balancing gut microbiota in STC. Overall, Leven PRO-CR alleviated slow-transit constipation potentially by enhancing 5-HT secretion, upregulating TPH1 channels, and restoring microbiota balance.
Curcumin mitigates testicular ischemia-reperfusion injury by suppressing NLRP3-mediated pyroptosis.
Hu Z, Wang J, Ning J … +1 more , Cheng F
Mol Immunol · 2025 Sep · PMID 40706257 · Publisher ↗
BACKGROUND: Testicular torsion results in damage by interrupting the blood supply. Nevertheless, the reestablishment of blood flow following testicular detorsion, a process known as testicular ischemia-reperfusion injury...
BACKGROUND: Testicular torsion results in damage by interrupting the blood supply. Nevertheless, the reestablishment of blood flow following testicular detorsion, a process known as testicular ischemia-reperfusion injury (IRI), often leads to further injury. Curcumin is a naturally occurring phenolic compound that has anti-inflammatory and antioxidant implications. It has been demonstrated to confer preventive implications in IRI between different organs. We propose ascertaining curcumin function in testicular IRI. METHODS: We created a mouse model to study testicular torsion/detorsion (T/D) and a germ cell model to study oxygen-glucose deprivation/reperfusion (OGD/R). The evaluation of testicular ischemia damage was conducted using histological staining. Testicular tissues were examined for the presence of reactive oxygen species (ROS) and pyroptosis-linked proteins employing western blot (WB), RT-qPCR, MDA, SOD assay kits, and immunohistochemistry analysis. Cell viability and cytotoxicity were measured via the Cell Counting Kit-8 (CCK-8) and LDH test kits. The amounts of inflammatory proteins were quantified employing ELISA, immunofluorescence, and immunoblotting methods. RESULTS: We observed that testicular IRI is involved in oxidative stress damage in cells, with an associated elevation in pyroptosis-linked proteins NLRP3 and caspase-1 (CASP-1) levels. Additionally, there is a rise in the inflammatory cytokines IL-1β and -18 levels. After treating with curcumin, we noted a significant inhibition of pyroptosis, particularly when the concentration was 20 μmol/L, where the inhibitory effect was most pronounced. Further investigation into the underlying mechanisms revealed that curcumin exerts its preventative implications against testicular IRI by targeting the NLRP3 pathway to suppress IRI-mediated pyroptosis. CONCLUSIONS: Curcumin mitigates testicular IRI-induced pyroptosis by modulating the NLRP3 signaling pathway, thereby alleviating cellular and tissue damage.
The impact of the role of cytokines on HIV infection in people living with HIV with and without comorbidities.
de Oliveira Souza N, Cortelette NA, Santos MP … +4 more , Dias-Baruffi M, Guimarães DAM, Ayres LR, Pancoto JAT
Mol Immunol · 2025 Sep · PMID 40700871 · Publisher ↗
Infection with the human immunodeficiency virus (HIV) causes a deterioration of the immune system. Changes in cytokine levels are seen in HIV infection and contribute to the pathogenesis of the disease. This study evalua...
Infection with the human immunodeficiency virus (HIV) causes a deterioration of the immune system. Changes in cytokine levels are seen in HIV infection and contribute to the pathogenesis of the disease. This study evaluated cytokine levels and single nucleotide polymorphisms (SNP) of genes associated with HIV infection and the development of comorbidities. The dosage of cytokines [(tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and interleukins (IL) 1, 6, 10 and 17)] were subjected to immunoenzymatic assays, and genotypes for TNF-α SNP -308 G/A, IFN-γ + 874 T/A, IL-1β -511 C/T, IL-6 -174 G/C and IL-10 -592 C/A by the polymerase chain reaction technique of the 200 enzymes used (CONT) and 200 people living with HIV (PLHIV). Relevant results were observed in the dosage of all as cytokines. There was an increase in the levels of TNF-α, IL-1β and IL-10 and a reduction in the levels of INF-γ, IL-6 and IL-17 in PLHIV compared to CONT. As the SNP demonstrated a predominance of the genotype of high TNF-α producer and low IFN-γ and IL-10 producers in the PLHIV group. Changes in the TNF-α, IFN-γ tests observed in the PLHIV group may be associated with the studied SNP, while the SNP IL-10 -592 C/A seems to indicate an association of this polymorphism with risk of HIV infection. Thus, investigations of the immunoregulatory mechanisms of HIV infection may be important in the establishment of new biomarkers for prognosis, in the discovery of new therapeutic targets, in the development of immunotherapies and in the results for curing the infection.
The relationship between Interleukin 1 beta single nucleotide polymorphisms and systemic lupus erythematosus among the Chinese Han population.
Liu M, Ling X, Tang Z … +5 more , Huang C, Wang P, Wu J, He Y, Chen J
Mol Immunol · 2025 Sep · PMID 40680524 · Publisher ↗
OBJECTIVE: Systemic lupus erythematosus (SLE) is a typical autoimmune disease whose etiology is related to genetic factors. This study is designed to evaluate the association between Single Nucleotide Polymorphisms (SNPs...
OBJECTIVE: Systemic lupus erythematosus (SLE) is a typical autoimmune disease whose etiology is related to genetic factors. This study is designed to evaluate the association between Single Nucleotide Polymorphisms (SNPs) of the Interleukin 1 beta (IL-1β) gene (rs16944, rs1143627, rs1143634) and SLE susceptibility and clinical characteristics in the Chinese Han population. METHODS: This case-control study recruited 155 SLE patients and 140 controls. DNA was extracted from the venous blood of all subjects and genotyped using PCR and mass spectrometry. RESULTS: Individuals with at least one mutant gene G (AG+GG genotype) at rs16944, at least one mutant gene A (AG+AA genotype) at rs1143627 and the AG Genotype at rs1143634 were associated with a lower risk of SLE compared to healthy controls(P = 0.009; P = 0.005; P = 0.016). The AG genotype at rs16944 increased the risk of anti-SSA(Ro) antibody positivity and thrombocytopenia (P = 0.033; P = 0.018), while the G allele decreased the risk of lupus nephritis (P = 0.040). For rs1143627, the A allele was linked with an increased risk of LA2 positivity for lupus anticoagulant (P = 0.041) and a lower risk of lupus nephritis (P = 0.044), and the AG genotype was associated with an increased risk of thrombocytopenia (P = 0.009). There was no correlation between rs1143634 and clinical features of SLE. CONCLUSION: In conclusion, IL-1β gene polymorphisms are related to SLE susceptibility and clinical features in the Chinese population.
Lithium: Emerging frontiers in metallopharmaceutical therapeutics.
Tong S, Xiao J, Zhang X … +1 more , Ma J
Mol Immunol · 2025 Sep · PMID 40680523 · Publisher ↗
The successful application of lithium salts in treating bipolar disorder marks a milestone in metallotherapeutics. Ongoing research has revitalized the clinical application of this "classic drug" lithium carbonate. Since...
The successful application of lithium salts in treating bipolar disorder marks a milestone in metallotherapeutics. Ongoing research has revitalized the clinical application of this "classic drug" lithium carbonate. Since the late 19th century, lithium salts have been found effective in improving bipolar disorder and established as a standard treatment. Recent studies highlight lithium's potential in neuroprotection, metabolic regulation, and cancer therapy due to its unique physicochemical properties. Its clinical applications continue to expand, demonstrating significant value in fields such as metalloimmunotherapy. This review summarizes the mechanisms of lithium and its growing role in treating diverse diseases.
GDF15 activates the PI3K/AKT pathway to mediate macrophage M2 polarization to promote prostate cancer resistance to docetaxel.
Li R, Wu H, Ran F … +5 more , He Y, Sun H, Peng W, Wang Q, Li J
Mol Immunol · 2025 Sep · PMID 40674958 · Publisher ↗
Drug resistance in cancer treatment is a major challenge, and macrophage polarization plays a key role in the development of prostate cancer (PCa). Growth differentiation factor 15 (GDF15) is highly expressed in most can...
Drug resistance in cancer treatment is a major challenge, and macrophage polarization plays a key role in the development of prostate cancer (PCa). Growth differentiation factor 15 (GDF15) is highly expressed in most cancers and is induced during anticancer treatment. The aim of this study was to investigate the regulatory mechanism of GDF15 in macrophage polarization and resistance to docetaxel (DTX) in PCa patients. We collected clinical samples from PCa patients to evaluate the expression level of GDF15 and its correlation with M2-type macrophage polarization. In this study, CCK-8, RTqPCR, flow cytometry and western blotting were used to investigate the mechanisms by which GDF15 regulates macrophage M2 polarization and PCa chemotherapy resistance. The results showed that GDF15 was significantly upregulated in PCa samples and was closely related to the level of M2 macrophage polarization. Further experiments revealed that M2 macrophages synthesize GDF15, which is involved in the regulation of DTX resistance in PCa cells. Following knockdown of GDF15 expression in M2-type macrophages, we observed that the resistance of PCa cells to DTX was significantly attenuated. This regulatory mechanism was achieved mainly through the inhibition of the PI3K/AKT signaling pathway, preventing the M2 polarization of macrophages. In conclusion, the upregulation of GDF15 in M2 macrophages can activate the PI3K/AKT signaling pathway, enhancing the DTX resistance of PCa cells. These findings provide new insights and potential targets for treatment strategies against PCa chemotherapy resistance.
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