Infection and Immunity最新文献

{"title":"Activation of macrophages by extracellular vesicles derived from <i>Babesia</i>-infected red blood cells.","authors":"Biniam Hagos, Ioana Brasov, Heather Branscome, Sujatha Rashid, Rebecca Bradford, Joseph Leonelli, Fatah Kashanchi, Choukri Ben Mamoun, Robert E Molestina","doi":"10.1128/iai.00333-24","DOIUrl":"https://doi.org/10.1128/iai.00333-24","url":null,"abstract":"<p><p><i>Babesia microti</i> is the primary cause of human babesiosis in North America. Despite the emergence of the disease in recent years, the pathogenesis and immune response to <i>B. microti</i> infection remain poorly understood. Studies in laboratory mice have shown a critical role for macrophages in the elimination of parasites and infected red blood cells (iRBCs). Importantly, the underlying mechanisms that activate macrophages are still unknown. Recent evidence identified the release of extracellular vesicles (EVs) from <i>Babesia</i> iRBCs. EVs are spherical particles released from cell membranes under natural or pathological conditions that have been suggested to play roles in host-pathogen interactions among diseases caused by protozoan parasites. The present study examined whether EVs released from cultured <i>Babesia</i> iRBCs could activate macrophages and alter cytokine secretion. An analysis of vesicle size in EV fractions from <i>Babesia</i> iRBCs showed diverse populations in the <100 nm size range compared to EVs from uninfected RBCs. In co-culture experiments, EVs released by <i>B. microti</i> iRBCs appeared to be associated with macrophage membranes and cytoplasm, indicating uptake of these vesicles <i>in vitro</i>. Interestingly, the incubation of macrophages with EVs isolated from <i>Babesia</i> iRBC culture supernatants resulted in the activation of NF-κB and modulation of pro-inflammatory cytokines. These results support a role for <i>Babesia</i>-derived EVs in macrophage activation and provide new insights into the mechanisms involved in the induction of the innate immune response during babesiosis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0033324"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763691","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 unique histidine kinase, AtcS, regulates motility and pathogenicity of the periodontal pathobiont, <i>Treponema denticola</i>.","authors":"Doaa N Abdallah, Annie N Hinson, Aidan D Moylan, Dhara T Patel, Bin Zhu, Richard T Marconi, Daniel P Miller","doi":"10.1128/iai.00112-25","DOIUrl":"https://doi.org/10.1128/iai.00112-25","url":null,"abstract":"<p><p><i>Treponema denticola</i> is an obligate colonizer of the human gingival crevice and, along with other pathobionts, is highly associated with the development of periodontal disease. As periodontal disease develops, significant environmental changes occur in the subgingival crevice and oral microbiome. The ability to sense and respond to changing environmental conditions is essential to the ability of <i>T. denticola</i> to thrive and cause disease. Yet, our understanding of <i>T. denticola</i> sensory transduction and gene regulatory mechanisms is nearly absent. The AtcSR two-component system has been predicted to regulate several cellular processes, but its role in <i>T. denticola</i> adaptive responses has not been investigated. To address this knowledge gap, we constructed a deletion of the <i>atcS</i> gene, encoding the histidine kinase. We performed RNA sequencing, demonstrating that the deletion of <i>atcS</i> results in significant changes in the transcriptome of <i>T. denticola</i>. Most notably, the transcription of genes encoding proteins involved in motility and the dentilisin protease complex was reduced. Consistent with this, the deletion mutant displayed reduced dentilisin activity and motility. These phenotypes are critical to interactions with host cells and the pathogenicity of <i>T. denticola</i>. This aligns with our observation that the <i>atcS</i>-deficient strain had attenuated attachment and invasion of gingival epithelial cells and failed to induce alveolar bone loss in a murine periodontitis model, processes that are central to <i>T. denticola</i> virulence. This study is a significant step toward defining the role of the AtcSR two-component system in <i>T. denticola</i> pathogenicity.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0011225"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763702","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":"Oral bacterium contributes to periodontal inflammation by forming advanced glycation end products.","authors":"Rajendra P Settem, Ashu Sharma","doi":"10.1128/iai.00560-24","DOIUrl":"https://doi.org/10.1128/iai.00560-24","url":null,"abstract":"<p><p>The oral bacterium <i>Tannerella forsythia</i> is associated with periodontitis, an inflammatory disease affecting tooth-supporting tissues. The bacterium produces a dicarbonyl compound, methylglyoxal (MGO), whose levels correlate with the severity of periodontitis. MGO can induce inflammation directly or via the generation of glycation products called advanced glycation end products (AGEs). <i>T. forsythia</i>-produced MGO has been shown to cause tissue collagen glycation, which in turn can induce pro-inflammatory cytokine secretion in monocytes via receptor for advanced glycation end product (RAGE) receptor activation. The current study investigated the impact of <i>T. forsythia</i>-secreted MGO on human gingival fibroblasts and endothelial cells. For assessing the <i>in vivo</i> impact of <i>T. forsythia</i>-secreted MGO, we employed an oral gavage-induced mouse model of periodontitis utilizing the wild-type and MGO-deficient strains of <i>T. forsythia</i>. Our results showed that the apoptotic activity was enhanced, and cell migration was reduced in fibroblasts exposed to collagen treated with the <i>T. forsythia</i> wild-type culture supernatant. Moreover, monocyte binding, reactive oxygen species production, and inflammatory cytokine secretion were increased in fibroblasts, and neutrophil transendothelial migration was enhanced in response to the <i>T. forsythia</i> wild type-treated collagen. <i>In vivo</i>, increased AGE accumulation in gingival tissues with increased alveolar bone loss was observed in wild-type <i>T. forsythia</i> as compared to the MGO-deficient strain-infected mice. These data demonstrated that <i>T. forsythia</i>-secreted MGO contributes to periodontal tissue destruction by mitigating gingival fibroblast-mediated tissue healing and promoting endothelial cell dysfunction. These findings provide a basis for targeting the <i>T. forsythia</i>-associated AGE-RAGE axis in alleviating periodontitis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0056024"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763698","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":"Arginine utilization in <i>Acinetobacter baumannii</i> is essential for pneumonia pathogenesis and is regulated by virulence regulator GacA.","authors":"Kuldip Devnath, Avik Pathak, Perwez Bakht, Ranjana Pathania","doi":"10.1128/iai.00572-24","DOIUrl":"https://doi.org/10.1128/iai.00572-24","url":null,"abstract":"<p><p>Nutrient availability in infection niches and the ability of bacterial pathogens to alter their metabolic landscape to utilize diverse carbon sources play a major role in determining the extent of pathogenesis. The vertebrate lung is rich in amino acids, such as arginine, which are available to the pathogens as a nutrient source to establish infection. Arginine is also used by the host nitric oxide synthase to synthesize nitric oxide, which is used against invading pathogens and for lung tissue repair. In this study, we have focused on the arginine catabolic pathway and its importance in the pathophysiology of <i>Acinetobacter baumannii</i>, a nosocomial pathogen, which is one of the major causes of ventilator-associated pneumonia, catheter-associated urinary tract infection, and so on. We show that the arginine succinyltransferase (AST) pathway is the predominant arginine catabolic pathway in <i>A. baumannii</i>. The genes of the AST pathway are arranged in an operon and are conserved in <i>Acinetobacter</i> spp. We show that the deletion mutant of the AST pathway failed to utilize arginine as a carbon source, and its virulence was severely compromised in an <i>in vivo</i> murine pneumonia infection model. We identified GacA as the positive regulator of the AST operon in <i>A. baumannii</i>, which is different from other bacterial pathogens. Our study highlights the importance of arginine utilization in the pathophysiology and virulence of <i>A. baumannii</i>. Owing to its importance in the pathophysiology of <i>A. baumannii</i>, the arginine catabolic pathway can further be investigated to assess its suitability as an antibacterial drug target.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0057224"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763694","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 probiotic <i>Lacticaseibacillus rhamnosus</i> GG supplementation reduces <i>Salmonella</i> load and modulates growth, intestinal morphology, gut microbiota, and immune responses in chickens.","authors":"Gary Closs, Menuka Bhandari, Yosra A Helmy, Dipak Kathayat, Dhanashree Lokesh, Kwonil Jung, Isidora D Suazo, Vishal Srivastava, Loic Deblais, Gireesh Rajashekara","doi":"10.1128/iai.00420-24","DOIUrl":"https://doi.org/10.1128/iai.00420-24","url":null,"abstract":"<p><p><i>Salmonella,</i> a leading cause of foodborne illnesses, is primarily transmitted to humans through the consumption of contaminated poultry products. The increasing resistance of <i>Salmonella</i> to antibiotics and lack of cross-protection by vaccines necessitate new control strategies in poultry production systems. This study assessed the efficacy of probiotics against <i>Salmonella</i> Typhimurium (ST) and <i>Salmonella</i> Enteritidis (SE). <i>Lactobacillus acidophilus</i> (LA), <i>Lacticaseibacillus rhamnosus</i> GG (LGG), and <i>Bifidobacterium animalis</i> subsp. lactis (Bb12) showed inhibition of ST and SE in agar well diffusion assay, with stable inhibitory properties. In co-culture assay, both LGG and Bb12 completely suppressed ST and SE growth. Liquid chromatography-with tandem mass spectrometry (LC-MS/MS) analysis of the LGG and Bb12 cell-free culture supernatant identified novel bioactive peptides with anti-<i>Salmonella</i> properties. Administering LGG in drinking water of chickens raised on built-up litter floor in experimental conditions significantly reduced the ST load (5.95 logs and 3.74 on 7 days post-infection [dpi] and 14 dpi, respectively). Gut microbiota analysis revealed increased abundance of several beneficial genera such as <i>Butyricicoccus</i>, <i>Erysipelatoclostridium</i>, <i>Flavonifractor,</i> and <i>Bacillus</i> in LGG-treated groups. Histomorphometry analysis demonstrated increased villus height (VH) and VH by crypt depth ratio in the ileum of the LGG-treated group on 14 dpi. These results highlight LGG as a promising probiotic for controlling <i>Salmonella</i> in chickens and reducing transmission to humans. The beneficial properties of LGG are attributed to the production of antimicrobial peptides, microbiota modulation, and enhanced intestinal integrity.IMPORTANCESalmonella is the leading cause of foodborne illnesses in the United States and worldwide. It is primarily transmitted through contaminated poultry and poultry products (eggs and poultry meat). Increasing resistance of Salmonella to antibiotics and lack of cross-protection by vaccines necessitate new control strategies to reduce Salmonella in poultry production system and minimize human infections. Probiotics, which are live beneficial microorganisms when administered in an optimum amount, have been increasingly used in recent years as alternatives to antibiotics to promote health. Our study showed that LGG exhibited superior probiotics properties and significantly reduced Salmonella load in chickens. Thus, LGG supplementation is a promising approach to prevent Salmonella infection and enhance performance of poultry thereby enhance food safety, proper antibiotic stewardship and public health.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0042024"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763653","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":"<i>Drosophila</i> symbionts in infection: when a friend becomes an enemy.","authors":"Yi Yu, Igor Iatsenko","doi":"10.1128/iai.00511-24","DOIUrl":"https://doi.org/10.1128/iai.00511-24","url":null,"abstract":"<p><p>The insect microbiome is comprised of extracellular microbial communities that colonize the host surfaces and endosymbionts that reside inside host cells and tissues. Both of these communities participate in essential aspects of host biology, including the immune response and interactions with pathogens. In recent years, our knowledge about the role of the insect microbiome in infection has increased tremendously. While many studies have highlighted the microbiome's protective effect against various natural enemies of insects, unexpected discoveries have shown that some members of the microbiota can facilitate pathogenic infections. Here, we summarize studies in the fruit fly, <i>Drosophila melanogaster</i>, that have substantially progressed our understanding of host-pathogen-microbiome interactions during infection. We summarize studies on the protective mechanisms of <i>Drosophila</i> gut microbiota, highlight examples of microbiome exploitation by pathogens, and detail the mechanisms of endosymbiont-mediated host protection. In addition, we delve into a previously neglected topic in <i>Drosophila</i> microbiome research-the crosstalk between endosymbionts and gut microbiota. Finally, we address how endosymbionts and gut microbiota remain resilient to host immune responses and stably colonize the host during infection. By examining how the microbiome is influenced by and reciprocally affects infection outcomes, this review provides timely and cohesive coverage of the roles of <i>Drosophila</i> endosymbionts and gut microbiota during infections.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0051124"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763688","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":"<i>Candida albicans</i> biofilm extracellular vesicles deliver candidalysin to epithelial cell membranes and induce host cell responses.","authors":"Sejeong Lee, Antzela Tsavou, Robert Zarnowski, Rita Pforte, Stefanie Allert, Thomas Krüger, Olaf Kniemeyer, Axel A Brakhage, Tam T T Bui, David R Andes, Jonathan P Richardson, Bernhard Hube, Julian R Naglik","doi":"10.1128/iai.00404-24","DOIUrl":"https://doi.org/10.1128/iai.00404-24","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are heterogeneous particles encapsulated with a phospholipid bilayer membrane. EVs have evolved diverse biological functions, serving mainly as prominent mediators and regulators of cell-cell communication. This study investigated whether candidalysin, a key virulence factor in <i>Candida albicans</i> infections, is present within EVs derived from <i>C. albicans</i> biofilms and retains activity by inducing host immune responses. We found that biofilm EVs contain candidalysin and can permeabilize planar lipid bilayer membranes in a dose-dependent manner. However, biofilm EVs were unable to damage oral epithelial cells (OECs) but were able to induce cytokine responses. Notably, EVs obtained from biofilms cultured for 24 h and 48 h exhibited differences in cargo composition and their ability to activate OECs. This study highlights the potential of biofilm EVs as a toxin delivery system during <i>C. albicans</i> infection and identifies temporal differences in the ability of EVs to activate epithelial cells.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0040424"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763680","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":"Probiotic colonization of <i>Xenopus laevis</i> skin causes short-term changes in skin microbiomes and gene expression.","authors":"Joseph D Madison, Owen G Osborne, Amy Ellison, Christina N Garvey Griffith, Lindsey Gentry, Harald Gross, Brian Gratwicke, Leon Grayfer, Carly R Muletz-Wolz","doi":"10.1128/iai.00569-24","DOIUrl":"https://doi.org/10.1128/iai.00569-24","url":null,"abstract":"<p><p>Probiotic therapies have been suggested for amelioration efforts of wildlife disease such as chytridiomycosis caused by <i>Batrachochytrium</i> spp. in amphibians. However, there is a lack of information on how probiotic application affects resident microbial communities and immune responses. To better understand these interactions, we hypothesized that probiotic application would alter microbial community composition and host immune expression in <i>Xenopus laevis</i>. Accordingly, we applied three amphibian-derived and anti-<i>Batrachochytrium</i> bacteria strains (two <i>Pseudomonas</i> spp. and one <i>Stenotrophomonas</i> sp.) to <i>X. laevis</i> in monoculture and also as a cocktail. We quantified microbial community structure using 16S rRNA gene sequencing. We also quantified genes involved in <i>X. laevis</i> immune responses using quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and skin transcriptomics over 1 and 3-week periods. All probiotic treatments successfully colonized <i>X. laevis</i> skin for 3 weeks, but with differential amplicon sequence variant (ASV) sequence counts over time. Bacterial community and immune gene effects were most pronounced at week 1 post-probiotic exposure and decreased thereafter. All probiotic treatments caused initial changes to bacterial community alpha and beta diversity, including reduction in diversity from pre-exposure anti-<i>Batrachochytrium</i> bacterial ASV relative abundance. Probiotic colonization by <i>Pseudomonas</i> probiotic strain RSB5.4 reduced expression of regulatory T cell marker (<i>FOXP3,</i> measured with RT-qPCR) and caused the greatest gene expression changes detected by transcriptomics. Single bacterial strains and mixed cultures, therefore, altered amphibian microbiome-immune interactions. This work will help to improve our understanding of the role of the microbiome-immune interface underlying both disease dynamics and emergent eco-evolutionary processes.IMPORTANCEAmphibian skin microbial communities have an important role in determining disease outcomes, in part through complex yet poorly understood interactions with host immune systems. Here we report that probiotic-induced changes to the <i>Xenopus laevis</i> frog skin microbial communities also result in significant alterations to these animals' immune gene expression. These findings underscore the interdependence of amphibian skin immune-microbiome interactions.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0056924"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763649","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":"Extracellular adherence proteins reduce matrix porosity and enhance <i>Staphylococcus aureus</i> biofilm survival during prosthetic joint infection.","authors":"Mohini Bhattacharya, Tyler D Scherr, Jessica Lister, Tammy Kielian, Alexander R Horswill","doi":"10.1128/iai.00086-25","DOIUrl":"10.1128/iai.00086-25","url":null,"abstract":"<p><p>Biofilms are a cause of chronic, non-healing infections. <i>Staphylococcus aureus</i> is a proficient biofilm-forming pathogen commonly isolated from prosthetic joint infections that develop following primary arthroplasty. Extracellular adherence protein (Eap), previously characterized in planktonic or non-biofilm populations as being an adhesin and immune evasion factor, was recently identified in the exoproteome of <i>S. aureus</i> biofilms. This work demonstrates that Eap and its two functionally orphaned homologs EapH1 and EapH2 contribute to biofilm structure and prevent macrophage invasion and phagocytosis in these communities. Biofilms unable to express Eap proteins demonstrated increased porosity and reduced biomass. We describe the role of Eap proteins <i>in vivo</i> using a mouse model of <i>S. aureus</i> prosthetic joint infection. The Results suggest that the protection conferred to biofilms by Eap proteins is a function of biofilm structural stability that interferes with the leukocyte response to biofilm-associated bacteria.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0008625"},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673773","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":"<i>Entamoeba gingivalis</i> induces gingival cell death, collagen breakdown, and host immune response via VAMP8/-3-driven exocytosis pathways.","authors":"Lea Rosenfeld, Nico Neumann, Xin Bao, Aysegül Adam, Arne S Schaefer","doi":"10.1128/iai.00005-25","DOIUrl":"https://doi.org/10.1128/iai.00005-25","url":null,"abstract":"<p><p>The protozoan <i>Entamoeba gingivalis</i> commonly colonizes anaerobic periodontal pockets, induces a severe innate immune response, invades gingival mucosa, and kills epithelial cells. <i>E. gingivalis</i> infection is associated with the common oral inflammatory disease periodontitis. DNA variants in vesicle-associated membrane proteins (VAMP) -3 and -8 genes are linked to increased periodontitis risk. These genes mediate host-pathogen interactions, including mucin exocytosis to form protective barriers and matrix metalloproteinase (MMP) secretion in intestinal amoebiasis caused by <i>Entamoeba histolytica</i>. This study aimed to investigate the roles of VAMP3/8 in gingival defense and <i>E. gingivalis</i> infection mechanisms. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing was used to create VAMP3/8-deficient gingival epithelial cells and fibroblasts. Functional analyses included immunofluorescence, enzyme-linked immunosorbent assay (ELISA), cytotoxicity, and collagenase assays. VAMP8 co-localized with mucins in gingival epithelial cells (gECs), and VAMP3 with MMPs in gingival fibroblasts. In gECs<i>, E. gingivalis</i> infection increased mucin (MUC1: 3.6×, MUC21: 14.4×) and interleukin secretion (IL-8, IL-1B: >6×, <i>P</i> = 0.019). <i>VAMP8</i> deficiency in gECs caused higher cell death (35% vs 4% in controls) with reduced exocytosis of mucins and interleukins. Likewise, <i>E. gingivalis</i>-induced VAMP8 translocation into lipid rafts was lost in VAMP8 knockout cells, validating the participation of VAMP8 in exocytosis. In wild-type but not VAMP3-deficient gingival fibroblasts, <i>E. gingivalis</i> strongly activated collagenases. <i>E. gingivalis</i> effects were more pathogenic than those of the oral anaerobic bacterium <i>Porphyromonas gingivalis. E. gingivalis</i> exploits VAMP8/3-driven exocytosis pathways, driving inflammation and tissue destruction, underscoring its role as a significant periodontal pathogen.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":" ","pages":"e0000525"},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673769","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}