Journal of Immunology Research最新文献

{"title":"The Molecular Mechanisms of Imatinib Treatment on Acute Lung Injury in Septic Mice Through Proteomic Technology.","authors":"Xiao Wang, ZhiQing Zhou, DuanYang Li, BoYang Zhang, XiaoLong Zong, Xue Liang, ZhenYu Li","doi":"10.1155/jimr/4526375","DOIUrl":"10.1155/jimr/4526375","url":null,"abstract":"<p><p><b>Background:</b> Acute lung injury (ALI) is the most common complication of sepsis. Despite considerable progress in the treatment of sepsis, the effective treatment strategies are lacking. A previous study has shown that imatinib reduces the rate of acute pulmonary damage in septic mice; however, the molecular mechanism remains unclear. Therefore, the current study aimed to investigate the potential mechanism by which imatinib alleviates ALI in septic mice. <b>Methods:</b> A septicemia model was established by intraperitoneal injection of lipopolysaccharide (LPS), followed by tail vein injection of imatinib in the treatment group. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors, and hematoxylin staining was used to detect pathological injury to the lung tissue. Tandem mass tag (TMT) quantitative labeling technology was used for proteomic sequencing analysis. The main target protein was identified through bioinformatics, and its expression was confirmed using western blotting. <b>Results:</b> We identified 128 differentially expressed proteins were associated with the protective effects of imatinib against septic lung injury. Functional enrichment analysis indicated that these proteins may be related to electron transfer, coagulation, and endothelial cell regulation in the oxidative respiratory chain. Enrichment of the nuclear factor-kappa B (NF-kB) signaling pathway, complement-coagulation cascade, and chemokine signaling pathway was also observed. Additionally, we found that the expression of CCAAT/enhancer-binding protein delta (CEBPD) and pyruvate dehydrogenase kinase 4 (PDK4) increased in the sepsis group but decreased in the imatinib group. <b>Conclusion:</b> Imatinib may reduce ALI in mice with sepsis by participating in oxidative respiratory and inflammatory responses, clotting response-related signaling pathways, and downregulating CEBPD and PDK4 expression.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"4526375"},"PeriodicalIF":3.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of Mitochondrial Fusion and Division in Harmine Derivative H-2-168-Induced Neurotoxicity.","authors":"Yuehong Gong, Meichi Pan, Hang Ren, Dongling Peng, Meiling Zhao, Yicong Zhao, Chunlin Luo, Qin Ma, Hao Wen, Jianhua Wang","doi":"10.1155/jimr/6678026","DOIUrl":"10.1155/jimr/6678026","url":null,"abstract":"<p><p><b>Background:</b> Harmine (HM) has several pharmacological effects; however, severe neurotoxicity limits its clinical application and development. HM neurotoxicity is associated with abnormal energy metabolism. This study aimed to explore the roles and underlying mechanisms of mitochondrial fusion and division in HM derivative H-2-168-induced neurotoxicity. <b>Methods:</b> PC12 cells were treated with H-2-168, Mdivi-1 (an inhibitor of mitochondrial division), or a combination of both. Cell viability, levels of reactive oxygen species (ROS), adenosine triphosphate (ATP), lactic dehydrogenase (LDH), mitochondrial morphology, and membrane potential were measured. Immunofluorescence (IF) and western blotting were used to determine the expression of apoptosis-, mitochondrial fusion-, and division-related proteins. Additionally, PC12 cells with Drp1 knockdown or Mfn2 overexpression were generated to explore their effects. <b>Results:</b> H-2-168 alone or in combination with Mdivi-1 significantly reduced PC12 cell viability, induced apoptosis, and impaired mitochondrial function. These effects were accompanied by increased levels of ROS and LDH, reduced ATP levels, upregulation of caspase-3, cytochrome c (Cyt-c), Drp1, and Fis1, and downregulation of Mfn2 and OPA1. Additionally, Drp1 knockdown or Mfn2 overexpression further enhanced the H-2-168-induced reduction in cell viability. <b>Conclusions:</b> These data implied that H-2-168 may initiate apoptosis in PC12 cells by influencing the balance between mitochondrial fusion and division, accompanied by changes in energy metabolism, which may induce neurotoxicity.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"6678026"},"PeriodicalIF":3.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibodies Against Vascular Endothelial Growth Factor A (VEGF-A) Reduce Synovitis, Bone Damage, and Osteogenesis in an SKG Mouse Model of Spondyloarthritis.","authors":"Marcin Czepiel, Małgorzata Stec, Anna Gąsiorek, Anna Gałuszka, Kornelia Kłosińska, Joanna Kozieł, Jarosław Czyż, Jarosław Baran, Przemysław Błyszczuk, Maciej Siedlar, Mariusz Korkosz","doi":"10.1155/jimr/8870895","DOIUrl":"10.1155/jimr/8870895","url":null,"abstract":"<p><p>Vascular endothelial growth factor-A (VEGF-A) plays a pivotal role in inflammatory rheumatic diseases, including spondyloarthritis (SpA). Recently, we have demonstrated that the expression of VEGF-A in human classical monocytes is positively associated with the number of swollen and painful joints in SpA patients. Therefore, we tested whether the anti-VEGF-A therapy can affect the hallmarks of SpA in the SKG mouse model. When initiated at the disease onset, the administration of anti-VEGF-A monoclonal antibodies (mAbs) significantly reduced the objective symptoms of SpA in the curdlan suspension-treated mice compared to their untreated and isotypic control-treated counterparts. Micro-computed tomography (CT) imaging revealed substantial benefits of the treatment, with anti-VEGF-A mAbs-treated mice exhibiting preserved joint spaces, reduced number and depth of bone erosions, and limited new bone formation in hind paws, calcaneus, sacroiliac joints, and caudal vertebrae. These effects remained in contrast to the pronounced damage and osteogenesis in relevant skeletal regions of control animals. The histological assessment confirmed reduced synovial inflammation and bone erosions in anti-VEGF-A mAbs-treated mice, underscoring the efficacy of the treatment in mitigating SpA bone damage. Collectively, anti-VEGF-A mAbs treatment favors the maintenance of joint and spine structures, alleviates bone destruction and osteogenesis, and reduces local inflammation in the mouse SpA model. Our study pinpoints anti-VEGF-A mAb therapy as a promising avenue to understand the SpA pathogenesis and as a treatment option. It also addresses vascular and inflammatory aspects of the disease and illustrates the potential of the SKG mouse SpA model for assessing the long-term safety of anti-VEGF-A therapy before its clinical translation.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"8870895"},"PeriodicalIF":3.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Th17/Treg Cell Imbalance May Contribute to Spontaneous Preterm Labor.","authors":"Meiyi Xu, Cunling Zhang, Dan Wu, Liying Yao, Mengyuan Geng, Shanshan Li, Yuling Guo, Qiushui Wang, Zhuo Wei, Wen Li","doi":"10.1155/jimr/8405365","DOIUrl":"10.1155/jimr/8405365","url":null,"abstract":"<p><p>Spontaneous preterm labor (SPTL) is a major cause of neonatal mortality and severe complications. T cells play a crucial role in mediating inflammation and immune tolerance at the maternal-fetal interface. T helper 17 cells (Th17, pro-inflammatory) and regulatory T cells (Treg, anti-inflammatory) are two subsets of CD4⁺ T cells with opposite functions, and their balance is important for maintaining immune homeostasis. Since infection and inflammation represent prominent factors responsible for the pathogenesis of SPTL, Th17/Treg imbalance at the maternal-fetal interface may trigger proinflammatory responses, potentially leading to SPTL. In this review, evidence from both clinical cases of SPTL and animal models indicates the presence of Th17/Treg imbalance in both peripheral blood and the maternal-fetal interface. Additionally, interleukin-6 (IL-6), interleukin-1<i>β</i> (IL-1<i>β</i>), and interleukin-8 (IL-8) have been involved in the pathogenesis of inflammation-induced SPTL, suggesting that Th17/Treg imbalance may have relevance to and be involved in the pathogenic process of SPTL. Moreover, the presence of Th17/Treg imbalance in risk factors for SPTL, such as autoimmune diseases and bacterial infections, further supports this connection indirectly. Although predictive models and interventional strategies related to SPTL have been explored, there is currently insufficient evidence to establish a direct causal relationship between Th17/Treg imbalance and the onset of SPTL.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"8405365"},"PeriodicalIF":3.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiretroviral Therapy at Conception Leads to Lower Peripheral CD49a⁺ NK Cells and Higher SERPINB2.","authors":"Yanling Huo, Jinhee Kim, Deborah Kacanek, Sadia Samer, Elizabeth G Livingston, Elizabeth Stankiewicz Machado, Elena Martinelli","doi":"10.1155/jimr/4771787","DOIUrl":"10.1155/jimr/4771787","url":null,"abstract":"<p><p><b>Problem:</b> Antiretroviral therapy (ART) during pregnancy is essential to prevent vertical HIV transmission and preserve the health of the mother and child. However, ART in pregnancy has been associated with adverse birth outcomes linked to poor placental development. Immune dysregulation of placental development is an important factor in the development of preeclampsia (PE), a common hypertension disorder of pregnancy. Some studies found an association between ART use at conception or during the first trimester and PE. However, little is known regarding the impact of timing of ART initiation on the immune environment in pregnancy. <b>Methods:</b> To investigate the immune environment in pregnant persons with HIV (PPWH) on ART at conception (<i>N</i> = 40) compared to PPWH that started ART in the second trimester (<i>N</i> = 40) we analyzed specimens from the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Perinatal Core Protocol, P1025, concluded in 2013. <b>Results:</b> No difference was found in soluble factors in circulation including PlGF and sFLt-1, associated with PE. However, upon analysis of PBMC by high dimension flow cytometry, we detected a lower frequency of circulating CD49a⁺ NK cells, associated with uterine tissue and pregnancy, in PPWH on ART at conception compared with PPWH who started ART in the second trimester. Moreover, PBMC from PPWH on ART at conception expressed higher levels of SERPINB2 in transcriptomics analyses. <b>Conclusions:</b> Our findings shed new insights into the potential impact of ART at conception and suggest the persistence of a dysregulated inflammatory environment compared to PPWH starting ART after the conclusion of placental development.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"4771787"},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen-E, Human Leukocyte Antigen-G Polymorphisms on Innate Immunity and COVID-19 Severity.","authors":"Cigdem Kekik, Sonay Temurhan, Yeliz Ogret, Behnoush Nasr Zanjani, Demet Kıvanc, Fatma Savran Oguz, Murat Kose, Fatma Betul Oktelik, Gunnur Deniz","doi":"10.1155/jimr/6691437","DOIUrl":"10.1155/jimr/6691437","url":null,"abstract":"<p><p><b>Background:</b> Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spans a spectrum of symptoms, ranging from mild respiratory issues to severe outcomes like pneumonia, acute respiratory distress syndrome, and fatality. Natural killer (NK) cells, governed by killer cell immunoglobulin-like receptors (KIRs), play a pivotal role in directly combating viral infections. Emerging studies indicate a decline in NK cell numbers and heightened NKG2A expression in infected individuals. <b>Objective:</b> This study focuses on genotyping human leukocyte antigen (HLA)-E, HLA-G, and KIR in SARS-CoV-2-positive individuals, comparing data between those with mild and moderate/severe symptoms. The cohort comprised 100 COVID-19-positive patients and 100 healthy volunteers, both groups subjected to DNA isolation and genotyping using sequence-based sequencing. <b>Results:</b> In 97 COVID-19-positive patients (52 mild, 24 moderate, and 21 severe) and 100 healthy volunteers, the study revealed protective associations with inhibitory alleles (KIR2DL1, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, and pseudo-alleles like KIR3DP1<i>⁣</i> ^<i>∗</i> 003). Conversely, predisposing factors included activator alleles (KIR2DS2, KIR3DS1) and pseudo-alleles (KIR3DP<i>⁣</i> ^<i>∗</i> 001/002). The G ^<i>∗</i> 01:04 allele and G ^<i>∗</i> 01:04-G ^<i>∗</i> 01:04 genotype emerged as protective, while the HLA-E ^<i>∗</i> 01:03-HLA-E ^<i>∗</i> 01:03 genotype may negatively impact disease prognosis. Conversely, the HLA-E ^<i>∗</i> 01:01-HLA-E ^<i>∗</i> 01:03 and HLA-E ^<i>∗</i> 01:01-HLA-E ^<i>∗</i> 01:01 genotypes may confer protection. <b>Conclusion:</b> Genetic variations in KIR, HLA-E, and HLA-G are associated with susceptibility and resistance to severe COVID-19 outcomes. This elucidates the intricate interplay of NK cells and immune-related genes, offering insights into potential therapeutic avenues and personalized approaches.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"6691437"},"PeriodicalIF":3.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: lncRNA PANTR1 Upregulates BCL2A1 Expression to Promote Tumorigenesis and Warburg Effect of Hepatocellular Carcinoma through Restraining miR-587.","authors":"Journal Of Immunology Research","doi":"10.1155/jimr/9874823","DOIUrl":"https://doi.org/10.1155/jimr/9874823","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1155/2021/1736819.].</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"9874823"},"PeriodicalIF":3.5,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression in the In Vitro Macrophage Expansion.","authors":"Yunpeng Wei, Jingzhao Yang, Wenhong Zu, Mengran Wang, Yong Zhao","doi":"10.1155/jimr/9994439","DOIUrl":"https://doi.org/10.1155/jimr/9994439","url":null,"abstract":"<p><p>Macrophages play essential roles in homeostasis and disease, and they were considered terminally differentiated cells that cannot proliferate. However, growing evidence shows that macrophages can self-renew in homeostasis and multiple pathological states in vivo and artificial induction in vitro. With the rise of immune cell therapy based on macrophages, large-scale in vitro expansion of macrophages has become more and more urgent. However, the proliferation of macrophages in vitro is still inefficient because of the heterogeneity of macrophages, complicated crosstalk between macrophages and their microenvironments, and poor understanding of macrophage proliferation regulations. In this review, we summarized the discoveries known to stimulate macrophage proliferation in vitro, including cytokines, small molecule compounds, metabolites, the composition of pathogens and apoptotic cells, natural product extracts, gene editing, and other factors, as well as related mechanisms. It can be concluded that the promotion of macrophage proliferation in vitro covers various approaches and mechanisms. However, it is still necessary to test more strategies and learn more macrophage proliferation mechanisms to achieve large-scale engineering expansion of macrophages in vitro.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"9994439"},"PeriodicalIF":3.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential Link Between Autoimmune Diseases and Pan-Cancer: A Multidatabase Mendelian Randomization Analysis.","authors":"Chenguang Wang, Zhiyong Liu, Yuhao Zhou, Yan He, Yashu Zhang, Shiqi Chen, Wenqing Yang, Lijun Fan","doi":"10.1155/jimr/6468979","DOIUrl":"10.1155/jimr/6468979","url":null,"abstract":"<p><p><b>Background:</b> The relationship between autoimmune diseases (AIDs) and cancer is unclear and this study aimed to investigate the relationship between AIDs and cancer at the genetic level using Mendelian randomization (MR). <b>Methods:</b> The study employed two-sample MR and meta-analysis to investigate the association between AIDs and 33 types of cancer, following STROBE-MR guidelines. Single nucleotide polymorphisms (SNPs) associated with AIDs were used as instrumental variables, with data from FinnGen, UK Biobank, and other databases. MR analyses included sensitivity checks, heterogeneity assessments, and reverse causality tests, using multiple MR methods (inverse-variance weighted (IVW), weighted median, MR-Egger, etc.). Meta-analysis was performed on validated results to confirm findings, with statistical analyses conducted using R software. <b>Results:</b> The results identified eight significant associations in both discovery and replication stages. Key findings include that myasthenia gravis (MG) significantly increases the risk of oral cavity cancer, multiple sclerosis (MS) is linked to increased risks of chronic lymphocytic leukemia (CLL) and small intestine cancer, and ulcerative colitis (UC) has mixed effects, reducing the risk of uterine cervix and larynx cancers, but increasing risks for pancreatic and bladder cancers. Meta-analysis confirmed eight secondary findings, highlighting pathogenic associations such as type 1 diabetes with esophagus cancer and protective effects like systemic lupus erythematosus (SLE) against acute myelocytic leukemia. <b>Conclusions:</b> This study provides evidence of a causal relationship between multiple AIDs and different cancer risks at the genetic level and provides a reference for the health management of patients with AIDs.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"6468979"},"PeriodicalIF":3.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Immunostimulatory Effects of Bacterial Lysate Proteins on THP-1 Macrophages: Pro-inflammatory Cytokine Response and Proteomic Profiling.","authors":"Md Mijanur Rahman, Asma Talukder, Md Sifat Rahi, Plabon Kumar Das, I Darren Grice, Glen C Ulett, Ming Q Wei","doi":"10.1155/jimr/2289241","DOIUrl":"https://doi.org/10.1155/jimr/2289241","url":null,"abstract":"<p><p>Bacterial lysate proteins (BLPs) serve as potential immunostimulants, recognized by pattern recognition receptors (PRRs) on immune cells, eliciting a robust immune response. In this study, THP-1 macrophages were treated with varying doses of BLPs derived from <i>Streptococcus pyogenes</i> (SP), <i>Streptococcus agalactiae</i> (SA), and <i>Serratia marcescens</i> (SM). The results showed significant increases (<i>p</i>  < 0.05) in pro-inflammatory cytokines such as TNF-<i>α</i>, IL-1<i>β</i>, IL-6, IL-12, granulocyte macrophage-colony stimulating factor (GM-CSF), eotaxin, and macrophage inflammatory protein (MIP)-1<i>α</i>, except for 5 µg of all BLPs for TNF-<i>α</i> and eotaxin, and 5 µg of SP for IL-12 production. No significant differences were found between the corresponding doses of SP and SA or SP and SM, except for GM-CSF in all doses, while SA and SM only showed a difference at the 5 µg dose for GM-CSF. Furthermore, there were no significant differences between the 10 and 20 µg doses of all BLPs, indicating that doses higher than 10 µg do not significantly enhance the pro-inflammatory response. Combination doses of SP + SM and SA + SM did not show significant differences, except for IL-1<i>β</i>, suggesting no synergistic effect. Cytotoxicity was observed to increase with higher BLP concentrations in a dose-dependent manner, with combinations of SP + SM and SA + SM exhibiting greater cytotoxicity than the individual BLPs. Proteomic analysis of BLPs identified immunostimulatory proteins, including heat shock proteins (HSPs; ClpB, DnaK, and GroEL), metabolic enzymes (glyceraldehyde 3-phosphate dehydrogenase (GAPDH), enolase, and arginine deiminase (ADI)), and surface and secreted proteins (ESAT-6-like protein, CRISPR-associated endonuclease Cas9, OmpA, porin OmpC, and serralysin), which are involved in immune modulation, bacterial clearance, and immune evasion. This study underscores the potential of bacterial proteins as vaccine adjuvants or supplementary therapies; however, further research is essential to find a balance between immune activation and inflammation reduction to develop safer and more effective immunostimulants.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"2289241"},"PeriodicalIF":3.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}