Innate Immunity最新文献

{"title":"Immunity's core reset: Synbiotics and gut microbiota in the COVID-19 era.","authors":"Dejana Bajić, Nemanja Todorović, Mladena Lalić Popović, Milica Plazačić, Andrea Mihajlović","doi":"10.1177/17534259251362023","DOIUrl":"10.1177/17534259251362023","url":null,"abstract":"<p><p>The gut microbiome plays a crucial role in shaping immune responses, and its connection to immunity has never been more relevant than in the COVID-19 era. The interaction between gut microbes and the immune system, known as microbiome-immunity crosstalk, influences both how the body responds to infections and how well it recovers. COVID-19, whether in its acute phase or lingering as long COVID, has been linked to disturbances in the gut microbiome. During infection, many patients experience dysbiosis-an imbalance in gut bacteria-that can contribute to immune dysfunction and excessive inflammation. This imbalance may not only worsen the severity of the disease but also prolong recovery, leading to persistent symptoms like fatigue, brain fog, and digestive issues. Long COVID, in particular, has been associated with ongoing immune dysregulation, where the body's defense system remains in a state of heightened activation, causing chronic inflammation. Given the strong link between gut health and immunity, there is growing interest in strategies to restore microbial balance. Synbiotics-combinations of probiotics (beneficial bacteria) and prebiotics (nutrients that support them)-are being explored as a potential therapeutic approach. By replenishing beneficial gut microbes, synbiotics may help regulate immune responses, reduce inflammation, and support overall recovery from COVID-19. Emerging research suggests that improving gut health could enhance the body's ability to fight infections and recover more efficiently. As we continue to understand the long-term impact of COVID-19, focusing on the gut microbiome offers a promising path forward. Supporting a balanced and diverse microbiome through diet, lifestyle, and targeted interventions like synbiotics may provide a natural way to strengthen immunity and improve health outcomes in both acute and long COVID cases.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251362023"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute-phase response- and inflammation-, but not extracellular matrix-related proteins in the amniotic fluid are associated with spontaneous preterm delivery in asymptomatic women with midtrimester short cervix.","authors":"Kyo Hoon Park, Bo Young Choi, Kyong-No Lee, Eunji Oh, Min Jung Lee, Hee Young Cho, Da Eun Jeong","doi":"10.1177/17534259251372138","DOIUrl":"10.1177/17534259251372138","url":null,"abstract":"<p><p><b>Background:</b> To determine whether (i) altered levels of acute-phase <i>response</i> (APR)-, inflammation-, and extracellular matrix (ECM)-related <i>proteins</i> in the amniotic fluid (AF) were associated with spontaneous preterm delivery (SPTD) in asymptomatic women with midtrimester short cervix (SCX) and (ii) if SPTD risk severity was related to the expression levels of inflammation-related proteins in the AF. <b>Methods:</b> This retrospective cohort study included 70 singleton pregnant women diagnosed with a SCX (<25 mm) at 17-25 weeks, who were subjected to amniocentesis to exclude intraamniotic inflammation (IAI; defined as AF interleukin [IL]-6 ≥ 2.6 ng/mL). APR (<i>i.e.,</i> h<i>epcidin,</i> kallistatin, MBL, pentraxin-2, RBP4<i>, and serpin A1)</i>, inflammatory (<i>i.e.,</i> <i>IL-6, IL-8, and resistin)</i>, and ECM-related (<i>i.e.,</i> lumican, MMP-8, TGFBI, and uPA) molecules were assayed in the AF by ELISA. The primary outcome measure was SPTD at <34 weeks. The levels of each identified dysregulated <i>inflammatory</i> mediator were divided into quartiles to assess the correlation between their AF expression profiles and SPTD risk severity. <b>Results:</b> Multivariable Firth logistic regression <i>analyses revealed that elevated AF levels of</i> IL-6, IL-8, kallistatin, pentraxin-2, <i>resistin,</i> and serpin A1, <i>and</i> IAI presence were independently associated with SPTD at <34 weeks after adjusting for baseline covariates. The areas under the curves of the aforementioned mediators ranged from 0.67 to 0.79 for outcome prediction. The odds of SPTD at <34 weeks, even after adjusting for confounders, significantly increased with each increasing quartile of baseline AF levels of IL-6/8, pentraxin-2, and resistin. <b>Conclusions:</b> APR (kallistatin, pentraxin-2, and serpin A1)- and inflammation (IL-6/8 and resistin)-, but not ECM-related mediators in the AF are involved in SPTD development in asymptomatic women with a midtrimester SCX. In particular, SPTD risk (especially risk severity) is associated with the degree of the inflammatory response in the AF, as categorized by inflammatory protein expression profiles, as well as IAI presence.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251372138"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathologic effect and immunomodulatory of <i>Indigofera oblongifolia</i> with silver nanoparticles against splenic injury by <i>Plasmodium chabaudi</i> infection in mice.","authors":"Mutee Murshed, Jameel Al-Tamimi, Hind Alzaylaee, Hani Ahmeda, Saleh Al-Quraishy","doi":"10.1177/17534259251396376","DOIUrl":"10.1177/17534259251396376","url":null,"abstract":"<p><p>Malaria, a globally prevalent disease caused by Plasmodium species, significantly impacts the immune system, particularly affecting splenic function. This study investigates the therapeutic potential of <i>Indigofera oblongifolia</i> leaf extracts (IOLE) with silver nanoparticles (AgNPs) against <i>Plasmodium chabaudi</i>-induced splenic damage in a female C57BL/6 mice model. Fifty female mice were infected with <i>P. chabaudi</i> and subsequently treated with IOLE AgNPs or chloroquine phosphate. Histopathological and immunohistochemical analyses revealed that IOLE AgNPs effectively restored splenic architecture, reduced inflammatory markers, and improved immune responses compared to the control and chloroquine-treated groups. These findings suggest that IOLE AgNPs may offer a novel therapeutic approach to mitigate splenic dysfunction associated with malaria and provide comparative analysis between established therapies like chloroquine and innovative combination of traditional medical plant and modern nano technology.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251396376"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12627400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bronchial pyroptosis promotes Th17 inflammation in steroid-insensitive asthma mouse.","authors":"Yun Lin, Jianhua Yin, Xia Yang, Jianghong Wei, Yaxi Liang, Chengfeng Zhou, Dongfang Zou, Shuyuan Chu","doi":"10.1177/17534259251372592","DOIUrl":"https://doi.org/10.1177/17534259251372592","url":null,"abstract":"<p><p>Bronchial cell pyroptosis and IL-17 respectively contribute- to the pathogenesis of steroid-insensitive asthma. In this study, we aim to explore the relationship between bronchial cell pyroptosis and Th17 in airway inflammation of steroid-insensitive asthma. The steroid-insensitive asthma model of mice was induced by toluene diisocyanate (TDI), which was also intraperitoneally injected with NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inhibitor MCC950. The bronchial epithelial cell pyroptosis was identified in morphology by transmission electron microscope. Protein expressions of pyroptosis cytokines (pro-Caspase-1, Caspase-1 p20, pro-GSDMD, cleaved-GSDMD and HMGB1), IL-17A, IL-17F and phosphorylated STAT3 (p-STAT3) in lung tissues were assessed by western blotting. Th17 in lung tissues was measured by flow cytometry. IL-17A + and p-STAT3 + cells in airway were identified by immunohistochemistry. In steroid-insensitive asthma mice, bronchial epithelial cell pyroptosis was confirmed in morphology using transmission electron microscope. Compared with controls, the protein expressions of Caspase-1 p20, cleaved-GSDMD and HMGB1 in lung tissues were increased in mice with steroid-insensitive asthma, which could be attenuated by MCC950. Th17 cells precentage and proteins expressions of p-STAT3, IL-17A and IL-17F were also increased in lung of steroid-insensitive asthmatic mice, which were also attenuated by MCC950. Similarly, the counts of IL-17A + cell and p-STAT3 + cell were more in airway of steroid-insensitive asthmatic mice than controls, and was attenuated by MCC950. In conclusion, bronchial epithelial cell pyroptosis could promote Th17 inflammation in airway of steroid-insensitive asthma mouse, which will provide further understanding on the interaction between innate immunity and acquired immunity in the pathogenesis of steroid-insensitive asthma.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251372592"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking mucosal innate immune responses to three influenza A virus strains in a highly translational pig model using nasopharyngeal swabs.","authors":"Helena A Laybourn, Charlotte Kristensen, Anders G Pedersen, Louise Brogaard, Sophie George, Betina L Henriksen, Chrysillis H Polhaus, Ramona Trebbien, Lars E Larsen, Kerstin Skovgaard","doi":"10.1177/17534259251331385","DOIUrl":"10.1177/17534259251331385","url":null,"abstract":"<p><p>BackgroundFour influenza pandemics have occurred during the past 100 years, and new variants of influenza viruses will continue to emerge. The nasal mucosa acts as the primary site of exposure to influenza A virus (IAV) infection, but viral recognition and host immune responses in the nasal mucosa are still poorly understood.ObjectivesThis study aimed to evaluate the utility of non-invasive nasopharyngeal swabs for longitudinal monitoring of mucosal immune responses in pigs experimentally challenged with two swine-adapted and one human-adapted IAV. By tracking antiviral immune responses from disease onset to recovery, we sought to assess the feasibility of this method for capturing dynamic changes in viral load and host responses across different IAV strains.MethodsForty-two IAV-negative pigs were divided into four groups and housed separately for infection studies. Viral and host RNA from nasopharyngeal swabs was analyzed using microfluidic qPCR, while statistical analysis was performed with a Bayesian approach in R. Additionally, immunohistochemical staining was used to assess MUC5AC expression in the nasal mucosa of infected pigs.ResultsRNA was successfully isolated from nasopharyngeal swabs, enabling gene expression analysis to monitor innate immune responses to IAV infection. A classical innate antiviral immune response was demonstrated after the three virus infections including expression of pattern recognition receptors (PRRs), transcription factors, interferons (IFNs), interferon-stimulated genes (ISGs), cytokines, and chemokines. The kinetics and magnitude of immune responses varied between infections, with notable downregulation of mucins following infection with the Danish swine-adapted isolate. Further, the Danish isolate induced a fast but transient IFN-mediated response concurrent with high expression of cytokines and chemokines, while the other swine-adapted Mexican isolate induced a prolonged immune response of ISGs, cytokines, and chemokines.ConclusionThis study highlights the significance of highly translational nasopharyngeal swabs as a non-invasive method for assessing mucosal antiviral immune responses. Utilizing microfluidic mRNA analysis, we gained valuable insights into antiviral mucosal responses across 216 swab samples collected from viral inoculation through recovery in three distinct influenza virus infections.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251331385"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipopolysaccharide preconditioning augments the antibacterial activity of renal macrophages and ameliorates acute kidney injury caused by <i>Staphylococcus aureus</i> bacteremia in mice.","authors":"Keiko Tanoue, Manabu Kinoshita, Bradley M Kearney, Seigo Ito, Hiroyasu Goto, Aoi Yamashiro, Tsugumi Fukunaga, Hiroki Sato, Kazuma Mori, Koji Kuwata, Hidehito Matsubara, Azusa Kato, Masahiro Nakashima, Hiroyuki Nakashima, Toshihiko Imakiire, Naoki Oshima","doi":"10.1177/17534259251335770","DOIUrl":"10.1177/17534259251335770","url":null,"abstract":"<p><p>IntroductionRepeated injections of low-dose lipopolysaccharide (LPS preconditioning) augment the antibacterial activity of liver macrophages. In this study, a mouse model of acute kidney injury (AKI) induced by <i>Staphylococcus aureus (S. aureus)</i> bacteremia was used to investigate the effects of LPS preconditioning on renal macrophages.MethodsEight-week-old C57BL/6J mice were preconditioned with either low-dose LPS (5 μg/kg) or the vehicle for three consecutive days. Kidney immune cells were isolated, and the antibacterial activity of renal macrophages was assessed by pHrodo^TM-labeled <i>S. aureus in vitro</i>. Twenty-four hours after the last LPS injection, the mice were intravenously challenged with <i>S. aureus</i> (2 × 10⁷ CFU) and their renal function was evaluated to identify the changes.ResultsMouse renal macrophages exhibited a weak antibacterial activity against <i>S. aureus</i> compared with the liver and spleen macrophages. LPS preconditioning elevated the count of F4/80^low CD11b^high bone marrow-derived macrophages (BMDM) and augmented their antibacterial activities in the mouse kidney. It also enhanced the antibacterial activity of F4/80^high CD11b^low tissue-resident macrophages (TRM) without altering their abundance. LPS preconditioning lowered the bacterial propagation in the kidney in the challenged mice and ameliorated sepsis-associated AKI compared with the control. LPS preconditioning upregulated the CD80/CD206 expression (M1/M2) ratio in BMDMs in the kidney before bacterial challenge and reduced their M1/M2 ratio following <i>S. aureus</i> challenge compared with the control.ConclusionLPS preconditioning enhanced the antibacterial activity of the renal macrophages against <i>S. aureus</i> and suppressed the excessive activation of M1 macrophages following <i>S. aureus</i> challenge, resulting in the amelioration of AKI caused by <i>S. aureus</i> bacteremia.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251335770"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-molecular-weight kininogen is a critical component of host defense against <i>Escherichia coli</i> sepsis.","authors":"Aizhen Yang, Yue Lu, Xiaofeng Yan, Meinan Peng, Miao Jiang, Yi Wu","doi":"10.1177/17534259251405951","DOIUrl":"10.1177/17534259251405951","url":null,"abstract":"<p><p>High-molecular-weight kininogen (HK) is known to bind lipopolysaccharides (LPS) with high affinity and serves as a crucial LPS carrier in circulation, supporting endotoxemia. However, its role in host defense against Gram-negative bacterial infection remains unclear. Here we demonstrate that HK directly binds to <i>Escherichia coli</i> (<i>E. coli</i>) via LPS and rapidly localizes to sites of infection. HK-deficient mice (<i>Kng</i>1<i>^-</i>^/-) showed increased susceptibility to infection, with increased bacterial dissemination, lung injury, and proinflammatory cytokine production. In contrast, endogenous expression of human HK in <i>Kng</i>1<i>^-</i>^/- mice restored survival, limited bacterial spread, and reduced tissue damage. Mechanistically, HK promoted neutrophil antimicrobial responses by enhancing reactive oxygen species production and microbicidal activity. Consistently, liver-specific HK deficiency recapitulated the impaired bacterial clearance and reduced survival upon <i>E. coli</i> challenge, highlighting the importance of plasma HK. Together, these findings identify HK as a new soluble pattern recognition molecule that senses <i>E. coli</i> invasion and initiates neutrophil-mediated antimicrobial responses, revealing a previously unrecognized protective function of the contact system in innate immunity.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251405951"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12708997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherent immunity and adaptive immunity: Mechanism and role in AECOPD.","authors":"Linguangjin Wu, Erxin Zhang, Yadan Tu, Yong Chen, Chenghu Wang, Yi Ren, Bangjiang Fang","doi":"10.1177/17534259251322612","DOIUrl":"10.1177/17534259251322612","url":null,"abstract":"<p><p>Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading cause of hospitalization and mortality in COPD patients. The occurrence of antibiotic resistance and the progression of non-infectious diseases contribute to poor patient outcomes. Thus, a comprehensive understanding of the mechanisms underlying AECOPD is essential for effective prevention. It is widely acknowledged that the immune system plays a fundamental role in pathogen clearance and the development of inflammation. Immune dysregulation, either due to deficiency or hyperactivity, has been implicated in AECOPD pathogenesis. Therefore, the purpose of this review is to investigate the possible mechanisms underlying dysregulated immune function and disease progression in COPD patients, specifically focusing on the innate and adaptive immune responses. The ultimate aim is to provide new insights for clinical prevention and treatment strategies targeting AECOPD.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251322612"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Rheumatic potential of biological DMARDS and protagonistic role of bio-markers in early detection and management of rheumatoid arthritis.","authors":"Muhammad Riaz, Ghulam Rasool, Ruhamah Yousaf, Hina Fatima, Naveed Munir, Hasan Ejaz","doi":"10.1177/17534259251324820","DOIUrl":"10.1177/17534259251324820","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects the synovial joint linings, resulting in progressive disability, increased mortality, and considerable economic costs. Early treatment with disease-modifying antirheumatic medications (DMARDs) can significantly improve the overall outlook for people with RA. Contemporary pharmaceutical interventions, encompassing standard, biological, and emerging small molecule disease- modifying anti-rheumatic medications continue to be the cornerstone of RA management, with substantial advancements made in the pursuit of achieving remission from the disease and preventing joint deformities. Nevertheless, a substantial segment of individuals with RA do not experience a satisfactory response to existing treatments, underscoring the pressing need for novel therapeutic options. Biologic DMARDs are among the therapy choices. Non-tumor necrosis factor inhibitors (Non-TNFi) such as abatacept, rituximab, tocilizumab, and sarilumab are examples, as are anti-tumor necrosis factor (TNF) medications such as infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol. More recent biomarkers have emerged and showed usefulness in the early detection of RA. These biomarkers, often referred to simply as \"biomarkers\", are quantifiable indicators of normal or pathologic processes, and they can also gauge treatment response. The assessment of RA treatment response typically combines patient-reported outcomes, physical evaluations, and laboratory findings, as there isn't a single biomarker that has proven sufficient for measuring disease activity. This review explores the usage of biologic DMARDs as a therapeutic approach for RA, as well as the biomarkers typically used for RA early diagnosis, prognosis prediction, and disease activity evaluation.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251324820"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPM2 deficiency contributes to M2b macrophage polarization via the PI3K/AKT/CREB pathway in murine sepsis.","authors":"Yanping Shen, Rana Dhar, Jujun Liu, Shenghui Hong, Huifang Tang, Xiaowei Qian","doi":"10.1177/17534259251343377","DOIUrl":"10.1177/17534259251343377","url":null,"abstract":"<p><p>BackgroundPrevious studies suggest that transient receptor potential melastatin 2 (TRPM2) plays a protective role in sepsis by enhancing bacterial clearance. This effect is mediated through the modulation of macrophage phenotypic changes, which strengthen the immune response against infection. However, the specific role and underlying mechanism of TRPM2 in macrophage polarization during sepsis remain unclear.MethodCecal ligation and puncture (CLP) was used to establish a mouse sepsis model, and bone marrow-derived macrophages (BMDMs) and peritoneal macrophages were prepared from C57BL/6 wild-type and TRPM2 knockout (<i>trpm</i>2^-/-) mice. IPI549 was utilized as a specific inhibitor of PI3K. Macrophage polarization, bactericidal ability, and the PI3K/protein kinase B (AKT)/cyclic adenosine monophosphate response element-binding protein signaling pathway were assessed. In addition, survival rate, bacterial burden, lung wet/dry weight ratio, lung and liver injury scores, and cytokine levels were measured in CLP-induced septic mice.ResultsIn lipopolysaccharide (LPS)-stimulated BMDMs, <i>trpm</i>2 deficiency increased the expression of characteristic markers associated with the M2b phenotype, reduced the bactericidal ability, and activated the PI3K/AKT/CREB signaling pathway. Consequently, both <i>trpm</i>2^-/- BMDMs and <i>trpm2</i>^-/- mice exhibited impaired bactericidal clearance during CLP-induced sepsis. Furthermore, IPI549 attenuated TRPM2 deletion-induced M2b polarization and restored the bactericidal function of BMDMs. Notably, IPI549 preconditioning reversed the increased susceptibility of the <i>trpm</i>2^-/- mice to sepsis. The 7-day mortality rate was 92% in <i>trpm</i>2^-/- mice, compared to 42% in IPI549-pretreated <i>trpm</i>2^-/- mice. Moreover, IPI549-treated mice exhibited improved lung wet/dry ratios, reduced lung and liver injury scores, reversed M2b polarization and decreased bacterial load.ConclusionThe PI3K/AKT/CREB pathway mediates the effect of TRPM2 by inhibiting M2b macrophage polarization and promoting bacterial clearance during sepsis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251343377"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}