Cytokine最新文献

{"title":"Serum levels of leucine-rich α–2 glycoprotein 1 (LRG1), pro-neurotensin (PNT), fatty acid-binding protein 4 (FABP4) and furin in pediatric growth hormone deficiency before and after 1-year growth hormone replacement therapy","authors":"Zhibo Zhou ,&nbsp;Yuxin Sun ,&nbsp;Zeyan Zheng ,&nbsp;Xiaoyuan Guo ,&nbsp;Hongbo Yang ,&nbsp;Shi Chen ,&nbsp;Hui Pan ,&nbsp;Huijuan Zhu","doi":"10.1016/j.cyto.2025.157022","DOIUrl":"10.1016/j.cyto.2025.157022","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate serum levels of leucine-rich α–2 glycoprotein 1 (LRG1), pro-neurotensin (PNT), fatty acid-binding protein 4 (FABP4), and furin in children with growth hormone deficiency (GHD) compared to idiopathic short stature (ISS) and healthy children, and to evaluate their changes and clinical relevance after 1-year growth hormone replacement therapy (GHRT).</div></div><div><h3>Methods</h3><div>The prospective cohort study was conducted in 32 idiopathic GHD, 32 ISS and 32 healthy children. Serum LRG1, PNT, FABP4, furin and clinical parameters were measured at baseline and after 6 and 12 months of GHRT. Correlation analyses were used to assess the associations between these adipokines and clinical variables. Restricted cubic spline curves and multivariable logistic regressions were used to assess the relationships between adipokines and GHD risk.</div></div><div><h3>Results</h3><div>At baseline, PNT and furin levels were significantly higher, while LRG1 was lower in GHD children compared to ISS and healthy controls. After 1-year GHRT, LRG1, PNT, FABP4, and furin levels significantly decreased in GHD patients. PNT levels were higher in male and GHD patients, and FABP4 levels were positively related with GV_SDS, BMI_SDS and negatively with FBG. Higher PNT levels were associated with increased GHD risks (OR = 15.545, <em>P</em> &lt; 0.001), while and higher LRG1 levels were associated with decreased GHD risks (OR = 0.291, <em>P</em> = 0.034).</div></div><div><h3>Conclusion</h3><div>GHD children have higher PNT and furin levels and lower LRG1 levels. During GHRT, LRG1, PNT, FABP4 and furin levels significantly decline, suggesting favorable metabolic effects and potential long-term benefits of GHRT.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"195 ","pages":"Article 157022"},"PeriodicalIF":3.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908940","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":"The NLRP3 inflammasome activation boosts lung injury, inflammation, and macrolide resistance in mycoplasma pneumoniae pneumonia","authors":"Meijun Zhu,&nbsp;Yan Lu,&nbsp;Yan Wei,&nbsp;Fei Hong,&nbsp;Juhua Ji,&nbsp;Lei Song","doi":"10.1016/j.cyto.2025.157014","DOIUrl":"10.1016/j.cyto.2025.157014","url":null,"abstract":"<div><div>The increase in the number of macrolide-resistant <em>Mycoplasma pneumoniae</em> (MP) poses a threat to human health worldwide. The present research investigates the role of the NLRP3 inflammasome in <em>mycoplasma pneumoniae</em> pneumonia (MPP). MPP patient (n = 40) and healthy control (n = 20)-derived serum samples were collected. MP (strain ATCC15531)-infected C57BL/6 J or Nlrp3^−/− mice with or without MCC950 treatment were used to explore the role of the NLRP3 inflammasome. The concentrations of inflammatory cytokines were determined by enzyme-linked immunosorbent assay. Histomorphological changes were determined by hematoxylin-eosin staining. The transcriptional and translational levels of NLRP3 were detected with quantitative PCR and western blot. Serum interleukin (IL)-1β and IL-18 levels were higher in MPP patients, along with elevated NLRP3 mRNA and protein levels. High NLRP3 expression was associated with fever duration, duration of admission, c-reactive protein and lactate dehydrogenase levels, and macrolide resistance. During the progression of MP infection, the NLRP3 inflammasome was progressively activated in mice, accompanied by increasing lung injury and inflammation. However, MP-infected Nlrp3^−/− mice showed decreased lung injury and inflammation. Additionally, MCC950 weakened lung injury and inflammation in MPP mice, and the combination of azithromycin and MCC950 exerted a stronger effect than azithromycin or MCC950 alone. The NLRP3 inflammasome activation boosts lung injury, inflammation, and macrolide resistance in MPP, implying that interfering with the NLRP3 inflammasome may be a stratagem for MPP administration.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"195 ","pages":"Article 157014"},"PeriodicalIF":3.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903009","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":"Aspergillus fumigatus and Mycobacterium tuberculosis synergistically induce TNF and IL-1β via different pathways in human peripheral blood mononuclear cells","authors":"Intan M.W. Dewi ,&nbsp;Mariolina Bruno ,&nbsp;Nico A.F. Janssen ,&nbsp;Mark S. Gresnigt ,&nbsp;Arjan van Laarhoven ,&nbsp;Reinout van Crevel ,&nbsp;Frank L. van de Veerdonk","doi":"10.1016/j.cyto.2025.157018","DOIUrl":"10.1016/j.cyto.2025.157018","url":null,"abstract":"<div><div><em>Aspergillus fumigatus</em> may cause infections in individuals with underlying lung damage, such as those with pulmonary tuberculosis (TB). Simultaneous exposure to <em>A. fumigatus</em> and <em>Mycobacterium tuberculosis</em> may worsen lung tissue damage, but the combined immune response to these pathogens has not yet been fully characterized.</div><div>Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were stimulated with <em>A. fumigatus</em> conidia, <em>M. tuberculosis</em> H37Rv lysate, or both combined. TNF and IL-1β were measured from culture supernatants. The role of different pattern recognition receptors (PRRs) important for the recognition of both pathogens were explored by using PRR inhibitors and PBMCs from donors deficient in certain pathways.</div><div><em>A. fumigatus</em> and <em>M. tuberculosis</em> synergistically induced TNF and IL-1β release by PBMCs, and this response was independent of TLR2 and dectin-1. We found that the synergy is regulated through distinct intracellular pathways. The activation of the intracellular receptor NOD2 by <em>M. tuberculosis</em> and NADPH oxidase complex-dependent ROS production triggered by <em>A. fumigatus</em> mediate TNF but not IL-1β synergy.</div><div>Together, these findings indicate that <em>A. fumigatus</em> and <em>M. tuberculosis</em> jointly exacerbate proinflammatory responses. This may help to explain the persistent inflammation and immunopathology observed in patients with concurrent TB and aspergillosis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"195 ","pages":"Article 157018"},"PeriodicalIF":3.7,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890853","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":"Blocking Fpr3 ameliorates osteoarthritis by inhibiting NLRP3-mediated chondrocyte pyroptosis","authors":"Bin Zhou,&nbsp;Yaobin Huang","doi":"10.1016/j.cyto.2025.157020","DOIUrl":"10.1016/j.cyto.2025.157020","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoarthritis (OA) is a chronic joint disorder that frequently diagnosed in elderly individuals. While formyl peptide receptor 3 (Fpr3) is known to play a significant role in inflammation, its involvement in OA progression and chondrocyte pyroptosis remains unclear.</div></div><div><h3>Methods</h3><div>Anterior cruciate ligament transection (ACLT) was used to create OA mouse model. Lipopolysaccharide (LPS) was utilized to induce inflammation in chondrocytes. We assessed the expression of Fpr3, chondrogenic markers (Collagen-II, SOX9, and Aggrecan), catabolic factors (MMP3, MMP13, and ADAMTS5), inflammatory cytokines (IL-1β, IL-18, and COX-2), and NLRP3 inflammasome members (NLRP3, ASC, Cleaved caspase1, and GSDMD-N) in cartilage from ACLT-induced mouse models and LPS-treated chondrocytes.</div></div><div><h3>Results</h3><div>Fpr3 expression was significantly increased in both ACLT-induced OA mice and LPS-induced chondrocytes. Fpr3 knockdown reduced chondrocyte injury in OA mice. Fpr3 knockdown promoted the expression of collagen-II, SOX9, and aggrecan, while suppressing the expression of MMP3, MMP13, ADAMTS5, IL-1β, IL-18, COX-2, NLRP3, ASC, cleaved caspase1, and GSDMD-N in both experimental models.</div></div><div><h3>Conclusions</h3><div>Blocking Fpr3 ameliorated extracellular matrix degradation and pyroptosis during OA progress through the NLRP3 inflammasome. Modulating Fpr3 expression may be a therapeutic target for OA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"195 ","pages":"Article 157020"},"PeriodicalIF":3.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885957","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":"The role of CXCL10 in cartilage development and diseases","authors":"Xi Cao ,&nbsp;Jianing Wu ,&nbsp;Jing Xie ,&nbsp;Jianxun Sun","doi":"10.1016/j.cyto.2025.157016","DOIUrl":"10.1016/j.cyto.2025.157016","url":null,"abstract":"<div><div>CXC motif chemokine ligand 10 (CXCL10), also known as interferon γ-induced protein 10 kDa, is a pleiotropic member of the CXC chemokine family and plays a potent role in cellular functions and pathophysiological processes, which include but are not limited to recruitment of immune cells, induction of cellular apoptosis, regulation of cell growth and proliferation, and inhibition of angiogenesis. The CXCL10/CXCR3 axis has been shown to initiate and promote a wide variety of cartilage diseases including rheumatoid arthritis (RA) and osteoarthritis (OA), and thus been considered as a potential biomarker for clinical prediction and monitoring. Moreover, with a strong ability to recruit mesenchymal stem cells to repair cartilage defects in joint lesions, CXCL10 is a promising candidate for cartilage tissue engineering. However, the understanding of CXCL10 on cartilage development, matrix synthesis and degradation, and joint disease progression is still largely limited. In this review, we systematically summarized the biological functions of CXCL10 and updated its latest progress in cartilage physiological and pathological processes, aiming to provide new clues for the treatment of cartilage diseases.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"195 ","pages":"Article 157016"},"PeriodicalIF":3.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863257","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":"Anti-inflammatory effect of probiotics in patients with Blastocystis spp. infection","authors":"Magda S.A. Abdeltawab ,&nbsp;Shimaa M. Abdel Aal ,&nbsp;Shaimaa Mohammed Ali ,&nbsp;Kerolos Y.W. Zaki ,&nbsp;Shimaa Saad El-Din ,&nbsp;Noha M. Amin","doi":"10.1016/j.cyto.2025.157013","DOIUrl":"10.1016/j.cyto.2025.157013","url":null,"abstract":"<div><div><em>Blastocystis hominis</em> BH infection has been linked to a variety of intestinal immunopathologies. Probiotic therapy is suggested to improve gastrointestinal inflammation during blastocystosis by inducing a pro-inflammatory cytokine response and modulating immune signaling pathways.</div><div>A hundred patients infected with BH were divided into 4 groups. Group 1: 20 patients did not receive any treatment; Group 2: 40 patients received probiotic therapy; Group 3: 20 patients received metronidazole; and Group 4: 20 patients received both metronidazole and probiotics. Metronidazole was administered at a dose of 250 mg three times daily for 10 days, whereas probiotic therapy consisted of Lacteol forte (<em>Lactobacillus acidophilus LB</em>) capsules twice daily for seven days. Patients were clinically evaluated for the outcome of gastrointestinal symptoms. In addition, fecal calprotectin (FCP) and tumor necrosis factor alpha (TNF-α) levels were measured by ELISA to assess intestinal inflammation and immune response.</div><div>Between-groups comparison for the presence of gastrointestinal symptoms after treatment did not show any significant difference except for the enhanced effect of probiotic therapy over metronidazole in relieving flatulence. Within-groups comparisons showed a significant reduction in the number of patients complaining of diarrhea in non-treated patients and in patients receiving combined treatment. A significant resolution of abdominal pain was observed among patients receiving probiotics. The number of patients suffering from flatulence significantly decreased in metronidazole and combined therapy-treated groups.</div><div>Assessment of FCP showed that the highest values were among non-treated patients, followed by patients receiving metronidazole, whereas the lowest values were detected in patients receiving probiotic therapy. As for the TNF-α levels, a significant reduction was observed in all patient groups.</div><div>Probiotic therapy alleviates intestinal inflammation in blastocystosis as indicated by the reduction of FCP and TNF-α after treatment and can also add a synergistic effect to that of metronidazole.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"195 ","pages":"Article 157013"},"PeriodicalIF":3.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860882","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":"Fowl adenovirus serotype 4 ORF1B protein suppresses type I interferon production by inhibiting IRF7 nuclear translocation","authors":"Shenyan Gao ,&nbsp;Saimin Zhai ,&nbsp;Ruixue Li ,&nbsp;Yameng Feng ,&nbsp;Linyang Yu ,&nbsp;Xiaozhan Zhang ,&nbsp;Zeng Wang","doi":"10.1016/j.cyto.2025.157017","DOIUrl":"10.1016/j.cyto.2025.157017","url":null,"abstract":"<div><div>Fowl adenovirus serotype 4 (FAdV-4), the causative agent of hepatitis-hydropericardium syndrome (HHS), has been reported to counter the host innate immune response. However, the underlying mechanisms employed by FAdV-4 to block cellular antiviral defense remain unclear. With a functional screen, we identified three FAdV-4 proteins that antagonized beta interferon (IFN-β) production induced by poly (dA:dT) and cGAS/STING in chicken fibroblasts. Specifically, the FAdV-4 unique nonstructural protein ORF1B exhibited the strongest inhibitory effect by targeting interferon regulatory factor 7 (IRF7). Further data found that ORF1B interacted with IRF7 to inhibit its nuclear translocation. Ectopic expression of IRF7 blocked the replication of FAdV-4, with virus titers and viral protein synthesis greatly lower than those of the control group. Conversely, knockdown of IRF7 promoted FAdV-4 replication in vitro. These findings illustrate the potential mechanism that allows FAdV-4 to evade host antiviral immunity.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"195 ","pages":"Article 157017"},"PeriodicalIF":3.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863258","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":"Dysregulation of the leukotriene pathway in Parkinson's disease: The potential role of montelukast","authors":"Sultan M. Alshahrani ,&nbsp;Hayder M. Al-kuraishy ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Mustafa M. Shokr ,&nbsp;Athanasios Alexiou ,&nbsp;Marios Papadakis ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.cyto.2025.157010","DOIUrl":"10.1016/j.cyto.2025.157010","url":null,"abstract":"<div><div>Leukotrienes (LTs) are inflammatory molecules released from leukocytes and mast cells that induce inflammation by activating leukocyte chemotaxis and vascular permeability. Notably, the LT pathway is implicated in the development and progression of different neurodegenerative diseases such as Parkinson's disease (PD). Preclinical research indicated that the LT pathway contributes to the pathophysiology of PD by inducing the development of neuroinflammation. The underlying causes for the exaggeration and over-activation of the LT pathway in PD are not completely clarified. Therefore, targeting the LT pathway may reduce the progression of neuroinflammation in PD. Besides, cysteinyl leukotriene receptor 1 (CysLT1R) antagonist montelukast has a neuroprotective effect against PD neuropathology by its antioxidant and anti-inflammatory effects; nevertheless, the exact role of montelukast in mitigating PD neuropathology is not fully explained. Consequently, this review aims to discuss the potential role of the LT pathway in PD pathogenesis and how montelukast alleviates PD neuropathology regarding the cellular and molecular effects.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"194 ","pages":"Article 157010"},"PeriodicalIF":3.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831277","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":"Circulating miRNAs and inflammatory markers – Associations between miRNAs and cytokine levels point to miRNA-mediated sCD40L release from platelets","authors":"Sandra Van der Auwera ,&nbsp;Sabine Ameling ,&nbsp;Anja Wiechert ,&nbsp;Nele Friedrich ,&nbsp;Matthias Nauck ,&nbsp;Henry Völzke ,&nbsp;Barbara M. Bröker ,&nbsp;Hans J. Grabe ,&nbsp;Uwe Völker","doi":"10.1016/j.cyto.2025.157012","DOIUrl":"10.1016/j.cyto.2025.157012","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are gaining increasing attention, particularly because of their involvement in immune-related signaling pathways. We investigated the association between 179 plasma-circulating miRNAs (Plasma Focus microRNA PCR Panel) and 47 cytokines (“MILLIPLEX® panel) in 692 participants of the population-based SHIP-TREND cohort (age range 21–79) and two additional cohorts to present a comprehensive map of miRNA-cytokine relations. Multivariate linear regression models identified Bonferroni-corrected significant associations between miRNAs and cytokines for EGF (pro-epidermal growth factor), PDGF-AA, PDGF-AB/BB (platelet-derived growth factor subunit A and B), VEGF-A (vascular endothelia growth factor A), and sCD40L (soluble CD40 ligand) with sCD40L showing the most robust pattern. These models were adjusted for age, sex, platelet count, BMI, smoking, and technical parameters. In the follow-up sample (<em>N</em> = 191, 7 years after initial sampling), we confirmed that the observed associations were stable over time and replicated our findings in an independent clinical cohort (<em>N</em> = 74). Furthermore, the causal mediation results provide evidence for the involvement of platelet activity in the regulation of sCD40L mediated by five miRNAs in the range of 25 %–69 % of the effect being mediated (strongest mediation for <em>hsa</em>-miR-223-3p). Our study highlights a strong and stable miRNA-mediated modulation of sCD40L, at the stage of platelet activation with potential subsequent effects on the interaction of immune cells and haemostasis pointing to a complex regulatory mechanism. Future research is needed to determine the clinical relevance of our observations in the context of vascular thrombosis, immunological disorders, and neurodegeneration.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"194 ","pages":"Article 157012"},"PeriodicalIF":3.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827449","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":"Manganese transport systems of two enteric bacteria enhance their resistance to stress and enable the bacteria to evade the innate immune responses","authors":"Xiao Wang ,&nbsp;Fuhua Zhang ,&nbsp;Qianqi Dai ,&nbsp;Yixin Zhao,&nbsp;Mohua Liu,&nbsp;Conghui Wu,&nbsp;Jingjing Tang,&nbsp;Yanchao Gu,&nbsp;Zhen Xie,&nbsp;Shukun Chen,&nbsp;Mengsi Zhang,&nbsp;Chunhui Luo,&nbsp;Xiao Wang,&nbsp;Yao Wang,&nbsp;Xihui Shen,&nbsp;Lei Xu","doi":"10.1016/j.cyto.2025.157009","DOIUrl":"10.1016/j.cyto.2025.157009","url":null,"abstract":"<div><div>Manganese (Mn) is an important element in bacteria-host interactions, exerting significant functions on both bacterial physiology and host immune responses. The importance of bacterial Mn transport systems in mediating bacterial stress resistance has been recognized, however, its role in modulating host innate immunity during infections remained elusive. This study aimed to explore the functions of the Mn transport proteins MntH and SitABCD in two enteric pathogens, Enterohemorrhagic <em>Escherichia coli</em> (EHEC) and <em>Salmonella enterica</em> serovar Typhimurium. We demonstrate that mutants deficient in these Mn uptake transporters (EHEC Δ<em>mntH</em> and <em>S. typhimurium</em> Δ<em>mntH</em>Δ<em>sitA</em>) exhibit markedly reduced resistance to extreme environmental conditions like oxidative stress and impaired competitive advantages. Importantly, EHEC Δ<em>mntH</em> and <em>S. typhimurium</em> Δ<em>mntH</em>Δ<em>sitA</em> elicited a significantly stronger innate immune response in macrophages compared to wild-type strains, indicating that MntH and SitABCD play a crucial role in inhibiting host immune activation. Specifically, we observed that Mn²⁺ enhanced the innate immune response to infection, and such an effect was abrogated in <em>cGas</em>^−/− and <em>Sting</em>^−/− macrophages. Importantly, MntH and SitABCD suppress innate immune response via the STING pathway. In conclusion, this study showed that the Mn transport systems in EHEC and <em>S. typhimurium</em> play important roles in modulating host immune responses, highlighting the importance of Mn availability in shaping the outcomes of enteropathogenic bacterial infections.</div></div><div><h3>Importance</h3><div>The manganese (Mn) transport systems MntH and SitABCD are crucial for bacterial survival. This study elucidates the role of Mn transport in enhancing bacterial resilience to oxidative stress and modulating the host's innate immune system, focusing on Enterohemorrhagic <em>Escherichia coli</em> (EHEC) and <em>Salmonella enterica</em> serovar Typhimurium. Our findings demonstrate that Mn uptake transporters not only confer stress resistance but also play a significant role in attenuating host immune activation through the STING signaling pathway. Mutants lacking MntH and SitABCD showed increased immune activation, suggesting these transporters help bacteria evade detection. The findings reveal that manganese not only enhances bacterial stress resistance but also modulates immune activation, thereby influencing infection outcomes.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"194 ","pages":"Article 157009"},"PeriodicalIF":3.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827611","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}