Cell Communication and Signaling最新文献

{"title":"Connexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.","authors":"Viola Donati, Chiara Di Pietro, Luca Persano, Elena Rampazzo, Mariateresa Panarelli, Clara Cambria, Anna Selimi, Lorenzo Manfreda, Ana Gabriela de Oliveira do Rêgo, Gina La Sala, Camilla Sprega, Arianna Calistri, Catalin Dacian Ciubotaru, Guang Yang, Francesco Zonta, Flavia Antonucci, Daniela Marazziti, Fabio Mammano","doi":"10.1186/s12964-025-02370-1","DOIUrl":"10.1186/s12964-025-02370-1","url":null,"abstract":"<p><strong>Background: </strong>Connexin (Cx) hemichannels (HCs) contribute to glioblastoma (GBM) progression by facilitating intercellular communication and releasing pro-tumorigenic molecules, including ATP and glutamate.</p><p><strong>Methods: </strong>The efficacy of abEC1.1, a monoclonal antibody that inhibits Cx26, Cx30, and Cx32 HCs, was assessed in vitro by measuring invasion capability, dye and Ca²⁺ uptake, glutamate and ATP release in patient-derived GBM cultures or organoids. Adeno-associated virus (AAV)-mediated antibody gene delivery, or convection-enhanced delivery (CED) of the purified antibody, was used in vivo to test the effect on tumor growth and animal survival, using a syngeneic GBM mouse model. The ability of the antibody to affect glioma-related hyperexcitability was evaluated by patch-clamp recordings in a 2D co-culture model comprising astrocytes and neurons isolated from mouse hippocampi, seeded with GL261 cells.</p><p><strong>Results: </strong>abEC1.1 suppressed GBM cell invasion, reducing gliotransmitter release, and impairing tumor progression. In patient-derived GBM cultures, abEC1.1 significantly decreased cell migration and ATP/glutamate release. In vivo, AAV-mediated antibody gene delivery or CED of the purified antibody reduced tumor burden and prolonged survival in the GL261 syngeneic mouse model of GBM. Furthermore, abEC1.1 mitigated glioma-induced excitatory synaptic activity in the 2D co-culture model, suggesting a dual role in tumor control and hyperexcitability suppression.</p><p><strong>Conclusions: </strong>Our findings establish Cx HC inhibition as a promising therapeutic avenue in GBM and highlight abEC1.1 as a potential candidate for clinical translation.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"391"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembled nanoparticle vaccine comprised of multiple epitopes provides robust protective immunity against reoviruses in fish model.","authors":"Fei-Fan Xu, Zhao Zhao, Zhu-Yang Deng, Jia-Lun Tang, Bin Zhu","doi":"10.1186/s12964-025-02411-9","DOIUrl":"10.1186/s12964-025-02411-9","url":null,"abstract":"<p><p>Grass carp reovirus type II (GCRV-II) has inflicted substantial economic damage to aquaculture industry due to highly contagious. To combat epidemic GCRV-II, we rational designed and constructed a multi-epitope nanoparticle vaccine (Pep-Fn) that consisted with cell penetrating peptide (CPP), epitope peptides, cell and grass carp-derived ferritin. Firstly, an anti-GCRV-II phage antibody library was constructed to screen antibodies for outer capsid proteins VP4 and VP35. Ab-1 and Ab-3 were successfully screened and demonstrated high affinity with GCRV-II particles. We further identified five potential epitopes (Pep1-Pep5) on the outer capsid protein recognized by Ab-1 and Ab-3 through protein-protein docking and alanine scanning mutagenesis. Then, a self-assembled nanoparticle displaying the Pep1-Pep5 and CPP on the surface was constructed for Pep-Fn preparation. Benefit from the nano-sized particle structure, Pep-Fn could overcome the body surface barrier and accumulate in the immune organs. Experiments demonstrated that Pep-Fn could effectively stimulate grass carp to produce anti-GCRV-II antibodies via immersion immunization and also provided protective effect against GCRV-II challenge. Collectively, our research provides a new vaccine design strategy for combating GCRV-II, and demonstrates the great potential of protein-based nanoparticle as a platform for GCRV-II vaccine development.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"389"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid overload meets S-palmitoylation: a metabolic signalling nexus driving cardiovascular and heart disease.","authors":"Jingwen Zhang, Suying Wu, Yuantong Xu, Lei Zhang, Cong Cong, Menghe Zhang, Yonghao Jiang, Yang Liu","doi":"10.1186/s12964-025-02398-3","DOIUrl":"10.1186/s12964-025-02398-3","url":null,"abstract":"<p><p>S-palmitoylation has emerged as a critical integrator of lipid overload and cardiovascular dysfunction. Disordered lipid metabolism inundates endothelial cells, vascular smooth muscle cells and macrophages with triglyceriderich lipoproteins, oxidized LDL and saturated fatty acids, expanding the intracellular palmitoylCoA pool and perturbing redox balance. Protein Spalmitoylation, the reversible attachment of palmitate to cysteine residues, converts excess palmitoylCoA into broad alterations in signalling and membrane dynamics. The FASN-ACSL-ZDHHC axis channel excess fatty acids into palmitoylCoA, which is transferred to pivotal proteins including the lipid transporter CD36, endothelial nitric oxide synthase (eNOS), key ion channels and the pyroptosis effector gasdermin D (GSDMD). Cycles of palmitate addition and removal regulate membrane residency, foam cell formation, nitric oxide production, calcium handling and inflammatory cell death, thereby linking lipid burden to atherosclerotic plaque growth, arrhythmogenic risk, heart failure progression and pulmonary hypertension. Therapeutic targeting of fatty acid uptake, palmitoyltransferases or thioesterases alleviates metabolic overload, restores endothelial reactivity and preserves myocardial viability in experimental models. This review synthesizes mechanistic and preclinical studies to delineate how lipiddriven protein palmitoylation reprograms cardiovascular physiology and pathology.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"392"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AXL and MERTK facilitate tissue repair in severe acute pancreatitis via a CCR5-dependent neutrophil and macrophage crosstalk.","authors":"Bin Li, Xiuli Zhang, Song Liu, Xiaoyu Guo, Wanyi Lu, Kaixin Peng, Rujuan Liu, Zhigao Chen, Liang Li, Guoyong Hu, Sohail Husain, Xingpeng Wang, Li Wen","doi":"10.1186/s12964-025-02412-8","DOIUrl":"10.1186/s12964-025-02412-8","url":null,"abstract":"<p><p>Severe acute pancreatitis (SAP) is a potentially life-threatening inflammatory disorder of the exocrine pancreas, characterized by massive cell death, which drives the progression and resolution of the disease. However, little is known about the key regulators in the tissue microenvironment that mediate tissue damage and repair. In this study, we discovered that AXL and MERTK in macrophages are responsible for tissue repair and pancreatic inflammation following SAP. Targeted deletion of Axl and Mertk in myeloid cells resulted in impaired phenotypic switch towards pro-resolving macrophage. This impairment is partly due to an accumulation of Cxcr2⁺ neutrophils and its interaction with Mrc1^+/high macrophages likely via CCL4-CCR5 axis. Pancreatic tissue repair was effectively restored by CCR5 inhibition. Collectively, we identify a CCR5-dependent pathway orchestrated by AXL and MERTK in macrophages, which offers a pharmacological target, to promote tissue repair in SAP.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"388"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting phase separation: a promising treatment option for hepatocellular carcinoma.","authors":"Ziling Zhou, Sikan Jin, Xiaoming Li, Dan Zhang, Shengxi Zhang, He Zhou, Ji Cai, Tao Song, Xianyao Wang, Qinghong Kong, Zhengzhen Tang, Jun Tan, Jidong Zhang","doi":"10.1186/s12964-025-02406-6","DOIUrl":"10.1186/s12964-025-02406-6","url":null,"abstract":"<p><p>The spontaneous phenomena known as liquid-liquid phase separation (LLPS) is caused by weak interactions between substances. Under specific circumstances, macromolecules like proteins and nucleic acids can dynamically aggregate to form biomolecular condensates. This phenomenon offers a novel perspective on the intricate spatiotemporal coordination within living cells. Recent research has shown that LLPS is crucial for the initiation and progression of cancer, mainly by influencing multiple cellular activities such as metabolism, autophagy, stress responses, immune reactions, transcriptional regulation and intracellular signaling pathways, etc. Dysregulation of LLPS significantly affects the proliferation, metastasis, and therapeutic resistance of hepatocellular carcinoma (HCC) cells. Here, we introduce recent advances in understanding how LLPS regulates HCC-associated signaling pathways. Furthermore, we discuss the molecular mechanisms underlying the LLPS of oncogenic signaling molecules and its potential implication. Finally, we summarize several feasible approaches for treating HCC by targeting LLPS. These findings have the potential to establish a novel theoretical framework and therapeutic hypothesis for cancer treatment, thus providing more precise and individualized clinical strategies and significantly enhance patient prognosis and overall survival rates.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"387"},"PeriodicalIF":8.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-gene CRISPR/cas9 library screen revealed targeting STAT6 increased the sensitivity of liver cancer to celecoxib via inhibiting arachidonic acid shunting.","authors":"Chujiao Hu, Zhirui Zeng, Xin Bao, Dahuan Li, Huading Tai, Haohao Zeng, Cheng Luo, Lei Tang, Tengxiang Chen, Shi Zuo","doi":"10.1186/s12964-025-02374-x","DOIUrl":"https://doi.org/10.1186/s12964-025-02374-x","url":null,"abstract":"<p><p>Celecoxib, a selective COX-2 inhibitor, has demonstrated anti-liver cancer effects in various preclinical models and clinical traits. However, prolonged use of celecoxib can lead to drug resistance, necessitating higher doses to maintain efficacy, which often results in severe side effects, limiting its clinical application. This study aimed to identify strategies to overcome celecoxib resistance in liver cancer. CRISPR/Cas9 screening revealed that liver cancer cells compensated for celecoxib treatment by upregulating ALOX and CYP enzymes, facilitating AA metabolism to produce alternative downstream products. STAT6 was identified as a key regulator of ALOX15, ALOX12, and CYP2E1, acting as a resister to celecoxib. Celecoxib stimulation leaded to increased phosphorylation of STAT6, enhanced binding to the promoters of target genes such as ALOX15, and upregulation of downstream gene expression. Knockdown of STAT6 significantly enhanced celecoxib sensitivity in vitro and in vivo by blocking AA shunting mediated by these enzymes. Furthermore, AS1517499, a STAT6 inhibitor, showed strong synergy with celecoxib in liver cancer cells by inhibiting AA shunting. In conclusion, targeting STAT6 enhances the efficacy of celecoxib in liver cancer by suppressing AA shunting. The combination of AS1517499 and celecoxib holds promise as a novel therapeutic strategy for liver cancer.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"384"},"PeriodicalIF":8.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.","authors":"Kai Wu, Jia Ji, Jingying Pan, Miaojin Zhu, Jiale Zhang, Ting Sun, Dan Lv, Mudan Wei, Minghai Wang, Hangping Yao","doi":"10.1186/s12964-025-02407-5","DOIUrl":"https://doi.org/10.1186/s12964-025-02407-5","url":null,"abstract":"<p><p>The liver is a crucial organ in the human body and is responsible for various functions, including digestion, detoxification, metabolism, and immune response. Proper hepatic function is vital for maintaining systemic homeostasis, and dysregulation of liver signaling pathways contributes to various diseases. Recepteur d'Origine Nantais (RON) is a transmembrane receptor tyrosine kinase that is activated by macrophage-stimulating protein (MSP) and coordinates cell fate decisions through the activation of downstream signaling cascades. As the predominant source of MSP in humans, the liver establishes a liver-specific MSP‒RON autocrine‒paracrine signaling axis that contributes to hepatic regeneration, metabolism, and immune functions. Extensive research has demonstrated that MSP-RON signaling is involved in steatotic liver diseases, hepatitis, cirrhosis, cholestatic liver disease, and liver cancer, highlighting the importance of RON in the development of liver diseases. This review demonstrates the role of the MSP-RON pathway both in maintaining liver homeostasis and in driving disease onset and progression while exploring its signaling mechanisms and therapeutic potential for liver disorders.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"385"},"PeriodicalIF":8.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intercellular signaling reinforces single-cell level phenotypic transitions and facilitates robust re-equilibrium of heterogeneous cancer cell populations.","authors":"Daniel Lopez, Darren R Tyson, Tian Hong","doi":"10.1186/s12964-025-02405-7","DOIUrl":"10.1186/s12964-025-02405-7","url":null,"abstract":"<p><strong>Background: </strong>Cancer cells within tumors exhibit a wide range of phenotypic states driven by non-genetic mechanisms, such as epithelial-to-mesenchymal transition (EMT), in addition to extensively studied genetic alterations. Conversions among cancer cell states can result in intratumoral heterogeneity which contributes to metastasis and development of drug resistance. However, mechanisms underlying the initiation and/or maintenance of such phenotypic plasticity are poorly understood. In particular, the role of intercellular communications in phenotypic plasticity remains elusive.</p><p><strong>Methods: </strong>In this study, we employ a multiscale inference-based approach that integrates single-cell transcriptomic data to predict phenotypic changes and tumor population dynamics. Our computational framework combines ligand-receptor interaction inference (CellChat), transcription factor activity estimation (decoupleR), and causal signaling network reconstruction (CORNETO) to analyze single-cell RNA sequencing (scRNA-seq) data and investigate how intercellular interactions influence cancer cell phenotypes, with a particular focus on EMT-related gene programs. We further use mathematical models based on ordinary differential equations, informed by network inferences, to examine how intercellular communication shapes phenotypic dynamics at the population level from a dynamical systems perspective.</p><p><strong>Results: </strong>Our inference approach reveals that signaling interactions between cancerous cells in small cell lung cancer (SCLC) result in the reinforcement of the phenotypic transition in single cells and the maintenance of population-level intratumoral heterogeneity. Additionally, we find a recurring signaling pattern across multiple types of cancer in which the mesenchymal-like subtypes utilize signals from other subtypes to support its new phenotype, further promoting the intratumoral heterogeneity. Our models show that inter-subtype communication both accelerates the development of heterogeneous tumor populations and confers robustness to their steady state phenotypic compositions.</p><p><strong>Conclusions: </strong>Our work highlights the critical role of intercellular signaling in sustaining intratumoral heterogeneity, and our approach of computational analysis of scRNA-seq data can infer inter- and intra-cellular signaling networks in a holistic manner.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"386"},"PeriodicalIF":8.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calreticulin in the nasal mucus promotes neutrophil migration and pathogen clearance.","authors":"Yichao Ma, Xinming Qin, Shiqi Liu, Ruoyang Lin, Baoyan Meng, Jian Lin, Qian Yang","doi":"10.1186/s12964-025-02388-5","DOIUrl":"https://doi.org/10.1186/s12964-025-02388-5","url":null,"abstract":"<p><p>The nasal cavity harbors diverse microbiota, and the nasal mucosal innate defense against microbial infiltration is crucial for respiratory infections. Both the nasal mucus covering the surface of the nasal cavity and the neutrophils beneath the nasal epithelia are the first line of innate defense against pathogens. Studying nasal mucus is challenging because of difficulties in collecting stable, high-quality samples from humans. Here, we investigated how nasal mucus cooperates with neutrophils to exert antimicrobial effects. Nasal mucus proteins, derived from nasal mucosal explants of goats, can promote neutrophil migration and increase their bactericidal activity. Calreticulin, identified from total mucus proteins, triggered ICAM-1-dependent transendothelial migration of neutrophils. Moreover, calreticulin activated the Rho GTPases of neutrophils via Toll-like receptor (TLR) 2 to promote their migration and further triggered the release of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) in a manner dependent on TLR2 and TLR4, accelerating the elimination of pathogens. In vivo studies also demonstrated that nasal inoculation with calreticulin induced neutrophil recruitment to the nasal mucosa and accelerated the clearance of Pasteurella multocida. Together, these findings highlight the synergistic interaction between nasal mucus and neutrophils as an important protective feature in the nasal mucosa.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"381"},"PeriodicalIF":8.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteroides dorei RX2020-derived bile acid alleviates influenza virus infection through TGR5 signaling.","authors":"Siqin He, Simin Lu, Tao Yang, Hanyu Ma, Yujia He, Jielan Mi, Kun Yue, Yuanming Huang, Liqiong Song, Yuchun Xiao, Zhihong Ren","doi":"10.1186/s12964-025-02384-9","DOIUrl":"https://doi.org/10.1186/s12964-025-02384-9","url":null,"abstract":"<p><strong>Background: </strong>The role of the gut microbiome in respiratory infections is increasingly recognized. We have found that a gut commensal strain, Bacteroides dorei RX2020 (B. dorei) previously isolated from healthy human fecal microbiota, alleviates influenza virus infection, but the underlying mechanisms remain elusive.</p><p><strong>Methods: </strong>To explore the mechanism by which B. dorei alleviates influenza, we administered it via gavage to influenza virus-infected mice. Gene knockout mice were then used to verify the underlying signaling pathways involved in the antiviral action of B. dorei. Metabolomics analysis was conducted to identify effective metabolites of B. dorei against influenza, followed by complementary verification to confirm these metabolites.</p><p><strong>Results: </strong>Metabolomics reveals that influenza virus infection significantly reduced the concentrations of secondary bile acid (BA) in feces at 7 post-infection (dpi). Oral administration of B. dorei increased bile salt hydrolase (BSH) activity and restored the BA metabolism, thereby protecting wild-type but not TGR5-deficient mice from influenza virus infection. B.dorei-mediated TGR5 activation inhibited influenza virus-induced lung inflammation via cAMP-PKA pathway. Supplementing exogenous Ursodeoxycholic acid (UDCA) and Hyodeoxycholic acid (HDCA), two metabolites changed dramatically after B. dorei treatment, reproduced the protective effect of B. dorei.</p><p><strong>Conclusions: </strong>Overall, our work elucidates the protective efficacy of commensal microbes against influenza virus infection by modulating lung immunity and restoring BA metabolism, suggesting a potential strategy to intervene in distal infections by regulating gut microbial metabolism.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"382"},"PeriodicalIF":8.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}