Molecular immunology最新文献

{"title":"Corrigendum to “miR-146a-5p targets IRAK1/TRAF6 to promote bacillus Calmette-Guérin survival by exosome-mediated autocrine actions” [Mol. Immunol. 185, Article number 7117]","authors":"Hao-Rong Chen , Huan-Shao Huang , Si-Yi Zeng , Yin-Fu Sun , Lan Chen , Shi-Ying Lai , Jia-Jun Wang , Fen Yang , Jiang Pi , Yan-guang Cong , Jun-Fa Xu","doi":"10.1016/j.molimm.2025.08.016","DOIUrl":"10.1016/j.molimm.2025.08.016","url":null,"abstract":"","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Page 146"},"PeriodicalIF":3.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formononetin ameliorates allergic asthma by inhibiting JUN and suppressing type Ⅱ immune responses mediated by ILC2 cells","authors":"Jian Liu ,&nbsp;Yanyan Li ,&nbsp;Meng Liu ,&nbsp;Xue Li ,&nbsp;Cheng Liu ,&nbsp;Yong Zhu","doi":"10.1016/j.molimm.2025.08.004","DOIUrl":"10.1016/j.molimm.2025.08.004","url":null,"abstract":"<div><h3>Objective</h3><div>Formononetin (FM), a flavonoid with potent anti-inflammatory effect, was investigated for its therapeutic potential and underlying mechanisms in allergic asthma (AS).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 114-123"},"PeriodicalIF":3.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DAP12 affects the acute inflammatory response caused by UPEC or LPS by regulating macrophage infiltration","authors":"Shuangshuang Sun ,&nbsp;Ruilin Yi ,&nbsp;Xiaoyu Wang ,&nbsp;Yixin Zhang ,&nbsp;Min Liu ,&nbsp;Luyue Wang ,&nbsp;Zihan Niu ,&nbsp;Ruiping Jia ,&nbsp;Zexuan Dong ,&nbsp;Huabao Xiong ,&nbsp;Changying Wang","doi":"10.1016/j.molimm.2025.08.006","DOIUrl":"10.1016/j.molimm.2025.08.006","url":null,"abstract":"<div><div>Urinary tract infection (UTI) is a prevalent bacterial infection, predominantly caused by uropathogenic <em>Escherichia coli</em> (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 <em>E. coli</em>, 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.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 124-132"},"PeriodicalIF":3.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NRF1 alleviates cerebral ischemia-reperfusion injury by transcriptionally activating FTO and downregulating m6A-mediated FOXO1 expression","authors":"Rongji Zou ,&nbsp;Fangfang Yu ,&nbsp;Maolin Wang ,&nbsp;Zhuopeng Jia","doi":"10.1016/j.molimm.2025.08.013","DOIUrl":"10.1016/j.molimm.2025.08.013","url":null,"abstract":"<div><h3>Background</h3><div>Studies show that upregulation of Nuclear respiratory factor 1 (NRF1) inhibits cerebral ischemia-reperfusion injury (CIRI). However, the molecular mechanism of NRF1 in CIRI remains to be largely unrevealed. Therefore, in this study, we aimed to investigate the potential mechanisms by which NRF1 regulates OGD/R-mediated neuronal apoptosis and its effects on CIRI in rats.</div></div><div><h3>Methods</h3><div>A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established to detect the expression of NRF1 in brain tissues of MCAO/R rats. Next, neuronal cells were treated with oxygen-glucose deprivation/reperfusion (OGD/R) and transfected with NRF1 overexpression vectors (pcDNA-NRF1), and cell apoptosis, inflammatory reaction and oxidative stress were evaluated. Furthermore, the enrichment of NRF1 in the promoter of fat mass and obesity-related genes (FTO) was evaluated with ChIP analysis, and the transcriptional activation of FTO by NRF1 was evaluated with luciferase reporter gene analysis. The m6A level of forkhead box O1 (FOXO1) mRNA was evaluated by MeRIP analysis, and the binding of FTO to FOXO1 mRNA was evaluated by RIP analysis. FTO siRNA and FOXO1 overexpression vectors (pcDNA-FOXO1) were transfected into NRF1 overexpressing neuronal cells to perform reversal experiments. Finally, MCAO/R rats were intracranially injected with NRF1 lentiviral vectors (LV-NRF1), and the volume of cerebral infarction, pathological damage and neuronal apoptosis were determined.</div></div><div><h3>Results</h3><div>NRF1 was downregulated in brain tissues of MCAO/R rats and OGD/R-treated neurons. Overexpression of NRF1 inhibited cell apoptosis and reduced inflammatory factor secretion (IL-1β and TNF-α) and oxidative stress (SOD activity was increased and MDA content was decreased) in OGD/R-treated neuronal cells. Mechanistic studies shown that NRF1 promotes FTO transcriptional activation by binding to the FTO promoter, while FTO interference upregulates FOXO1 expression by increasing the m6A level of FOXO1 mRNA. Silencing FTO or overexpression of FOXO1 reversed the inhibitory effect of NRF1 overexpression on OGD/R-induced neuronal damage. In addition, upregulation of NRF1 reduced the volume of cerebral infarction and alleviated neurological impairment and neuronal apoptosis in MCAO/R rats.</div></div><div><h3>Conclusions</h3><div>This study revealed that NRF1 inhibited neuronal apoptosis and alleviated neurological deficits and neuro-inflammation in MCAO/R rats by promoting FTO-m6A-mediated downregulation of FOXO1, which may provide a potential therapeutic strategy for CIRI.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 133-145"},"PeriodicalIF":3.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sigmoidin B attenuates sepsis-associated encephalopathy through EZH2-AKT2-mediated regulation of microglial polarization","authors":"Ziyi Wang ,&nbsp;Yafei Liu ,&nbsp;Yuxin Liu ,&nbsp;Qingcheng Li ,&nbsp;Zhong Wang ,&nbsp;Dongliang Mu","doi":"10.1016/j.molimm.2025.08.010","DOIUrl":"10.1016/j.molimm.2025.08.010","url":null,"abstract":"<div><h3>Purpose</h3><div>Enhancer of zeste homolog (EZH2) is a potential target in treatment of sepsis. The current study is aimed to screen a novel EZH2 degrader agent based on the Traditional Chinese Medicine Database YaTCM. This may provide an important clue for development of new drugs to treat sepsis-associated encephalopathy (SAE).</div></div><div><h3>Methods</h3><div>Macrophage-specific EZH2 knockout mice were used to observe the effects of EZH2 on the survival rate, levels of inflammatory cytokines, S100B, CD86, and CD206 in sepsis mice. Sigmoidin B was screened as the novel EZH2 degrader based on the structure of MS177 using large-scale virtual high-throughput screening. Molecular dynamics simulations and MMGBSA analysis were used to assess the stability and binding characteristics of Sigmoidin B. The protective effect of MS177 and the novel EZH2 degrader were verified using in vivo and vitro experiments.</div></div><div><h3>Results</h3><div>Macrophage-specific knockout of EZH2 had been shown to enhance the survival rate in mice with sepsis, reduce levels of CD86 and TNF-α, promote the expression of IL-10 and CD206, and mitigate the extent of brain injury. Sigmoidin B exhibited strong binding affinity to EZH2 and featured a flavonoid core structure along with an olefin side chain. Molecular validation experiments confirmed that Sigmoidin B could ameliorate cognitive dysfunction and modulate microglial polarization via the EZH2-AKT2 pathway. Notably, Sigmoidin B demonstrated superior efficacy compared to MS177 in alleviating inflammation.</div></div><div><h3>Conclusion</h3><div>Natural compound Sigmoidin B was successfully screened and confirmed as a novel EZH2 degrader, which was a potential target for the development of new therapeutic for SAE.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 95-113"},"PeriodicalIF":3.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALKBH5-mediated m6A demethylation modification of RAD51 inhibits osteogenic differentiation via promoting DNA damage in osteoporosis","authors":"Minli Qiu ,&nbsp;Zetao Liao ,&nbsp;Xinyu Wu ,&nbsp;Peili He ,&nbsp;Xianghui Wen ,&nbsp;Ya Xie ,&nbsp;Jun Qi","doi":"10.1016/j.molimm.2025.08.008","DOIUrl":"10.1016/j.molimm.2025.08.008","url":null,"abstract":"<div><div>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 <em>RAD51</em> 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 <em>in vitro</em> 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 m⁶A 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 <em>RAD51</em> and AlkB Homolog 5 (<em>ALKBH5</em>)/YTH domain family (<em>YTHDF)1</em> was validated through RNA immunoprecipitation and dual-luciferase reporter assays. Results demonstrated that <em>ALKBH5</em>-mediated m⁶A demethylation significantly suppressed <em>RAD51</em> expression in MC3T3-E1 cells. Furthermore, <em>ALKBH5</em> knockdown enhanced osteoblast differentiation by alleviating DNA damage. Mechanistically, the <em>ALKBH5/YTHDF1</em> m⁶A regulatory axis modulated <em>RAD51</em> mRNA stability through m⁶A methylation dynamics. <em>In vivo</em> experiments revealed that <em>ALKBH5</em> deletion mitigated bone loss and promoted osteoblastogenesis in OVX mice through inhibition of DNA damage pathways. Collectively, these findings indicated that <em>ALKBH5</em>-mediated m⁶A demethylation of <em>RAD51</em> inhibited osteogenic differentiation by inducing DNA damage in OP, suggesting potential therapeutic targets for osteoporosis treatment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 82-94"},"PeriodicalIF":3.0,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of immunogenic cell death-related genes is correlated with the immune microenvironment and predicts prognosis in lung adenocarcinoma","authors":"Fushan Gao ,&nbsp;Yin Liang ,&nbsp;Wenlin Gong","doi":"10.1016/j.molimm.2025.08.005","DOIUrl":"10.1016/j.molimm.2025.08.005","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 70-81"},"PeriodicalIF":3.0,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of long-distance transport on glycolipid metabolism and immune function in simmental calves","authors":"Cailin Xu ,&nbsp;Yijia Zhou ,&nbsp;Zhenbang Ye,&nbsp;Yang Ni,&nbsp;Xueshu Han,&nbsp;Yuning Liu,&nbsp;Zhenjun Sun,&nbsp;Huanqi Liu,&nbsp;Yongping Chen","doi":"10.1016/j.molimm.2025.08.007","DOIUrl":"10.1016/j.molimm.2025.08.007","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 63-69"},"PeriodicalIF":3.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bta-miR-25 alleviates lipopolysaccharide-induced endometritis in cows by targeting DUSP10 to inhibit MAPK signaling","authors":"Zhihao Zhang ,&nbsp;Xiangnan Wang ,&nbsp;Qiao ting Shi ,&nbsp;Li gang Lu ,&nbsp;Xiang zhou Yan ,&nbsp;Xingshan Qi ,&nbsp;Zi jing Zhang ,&nbsp;Er yao Wang","doi":"10.1016/j.molimm.2025.07.015","DOIUrl":"10.1016/j.molimm.2025.07.015","url":null,"abstract":"<div><div>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 <em>in vitro</em> endometritis model was constructed using LPS. The expression levels of proinflammatory cytokines <em>IL-6, IL-8, IL-1β, and TNF-α</em> 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 <em>DUSP10</em> 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 <em>DUSP10</em> also inhibited the LPS-induced increase in inflammatory factors. In summary, bta-miR-25 can inhibit LPS-induced endometritis by over the expression of <em>DUSP10</em>. bta-miR-25 and <em>DUSP10</em> may serve as biomarkers and potential therapeutic targets for endometritis in dairy cows.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 39-47"},"PeriodicalIF":3.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gelatin enhances bacteria-phagocytosis via a ROS-mitochondria-STING axis in differentiated human macrophage-like U937 cells","authors":"Xiaoli Sun ,&nbsp;Meiling Li ,&nbsp;Yuhang Ma ,&nbsp;Kaihui Chen ,&nbsp;Shunuo Jiang ,&nbsp;Toshihiko Hayashi ,&nbsp;Kikuji Itoh ,&nbsp;Kazunori Mizuno ,&nbsp;Shunji Hattori ,&nbsp;Hitomi Fujisaki ,&nbsp;Weiwei Liu ,&nbsp;Takashi Ikejima","doi":"10.1016/j.molimm.2025.08.011","DOIUrl":"10.1016/j.molimm.2025.08.011","url":null,"abstract":"<div><div>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 <em>Escherichia coli</em> and Gram-positive <em>Staphylococcus aureus</em>. 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.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 48-62"},"PeriodicalIF":3.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}