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":"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":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070731/pdf/","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":"OA","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":"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":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070737/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Species-specific components of the <i>Helicobacter pylori</i> Cag type IV secretion system.","authors":"Kaeli N Bryant, Arwen E Frick-Cheng, Lauren E Solecki, Heather K Kroh, W Hayes McDonald, D Borden Lacy, Mark S McClain, Melanie D Ohi, Timothy L Cover","doi":"10.1128/iai.00493-24","DOIUrl":"10.1128/iai.00493-24","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> strains containing the <i>cag</i> pathogenicity island (PAI) deliver an effector protein (CagA) and non-protein substrates into gastric cells through a process that requires the Cag type IV secretion system (T4SS). The Cag T4SS outer membrane core complex (OMCC) contains multiple copies of five proteins, two of which are species-specific proteins. By using modifications of a previously described OMCC immunopurification method and optimized mass spectrometric methods, we have now isolated additional <i>cag</i> PAI-encoded proteins that are present in lower relative abundance. Four of these proteins (CagW, CagL, CagI, and CagH) do not exhibit sequence relatedness to T4SS components in other bacterial species. Size exclusion chromatography analysis of immunopurified samples revealed that CagW, CagL, CagI, and CagH co-elute with OMCC components. These four Cag proteins are copurified with the OMCC in immunopurifications from a Δ<i>cag3</i> mutant strain (lacking peripheral OMCC components), but not from a Δ<i>cagX</i> mutant strain (defective in OMCC assembly). Negative stain electron microscopy analysis indicated that OMCC preparations isolated from Δ<i>cagW, cagL::kan,</i> Δ<i>cagI, and</i> Δ<i>cagH</i> mutant strains are indistinguishable from wild-type OMCCs. In summary, by using several complementary methods, we have identified multiple species-specific Cag proteins that are associated with the Cag T4SS OMCC and are required for T4SS activity.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"93 5","pages":"e0049324"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965374","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 protein degradation system encoded by <i>hslUV</i> (<i>ClpYQ</i>) is dispensable for the virulence of <i>Haemophilus ducreyi</i> in human volunteers.","authors":"Kate R Fortney, Julie A Brothwell, Teresa A Batteiger, Rory Duplantier, Barry P Katz, Stanley M Spinola","doi":"10.1128/iai.00577-24","DOIUrl":"10.1128/iai.00577-24","url":null,"abstract":"<p><p><i>Haemophilus ducreyi</i> causes cutaneous ulcers in children who live in yaws-endemic countries and the genital ulcer disease chancroid. In the human host, <i>H. ducreyi</i> resides in an abscess and may need to resist both heat and oxidative stress, which result in aggregation and misfolding of bacterial proteins. In <i>Escherichia coli</i>, the <i>hslUV</i> (<i>clpYQ</i>) operon encodes a proteasome-like complex that degrades misfolded proteins and is upregulated during heat shock. In previous studies, we showed that <i>hslUV</i> transcripts are upregulated in experimental lesions caused by <i>H. ducreyi</i> in human volunteers, suggesting that HslUV may help <i>H. ducreyi</i> adapt to the abscess environment. Here, we constructed an unmarked <i>hslUV</i> operon deletion mutant, 35000HPΔ<i>hslUV</i>, in <i>H. ducreyi</i>. Whole-genome sequencing showed that compared to its parent (35000HP), the mutant contained only the deletion of interest. Six volunteers were inoculated at three sites on skin overlying the deltoid on opposite arms with 35000HP and 35000HPΔ<i>hslUV</i>. Within 24 h, papules formed at 88.9% (95% CI [69%, 100%]) at both parent and mutant-inoculated sites (<i>P</i> = 1.0). Pustules formed at 44.4% (95% CI [25.6%, 64.3%]) at parent-inoculated sites and 33.3% (95% CI [2.5%, 64.1%]) at mutant-inoculated sites (<i>P</i> = 0.17). Thus, the proteosome-like complex encoded by <i>hslUV</i> was dispensable for <i>H. ducreyi</i> virulence in humans. In the absence of <i>hslUV</i>, <i>H. ducreyi</i> likely utilizes other systems such as the Lon protease, ClpXP, and ClpB/DnaK to combat protein aggregation and misfolding, underscoring the importance of the functional redundancy of such systems in gram-negative pathogens.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"93 5","pages":"e0057724"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970092","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":"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":"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":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070732/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cranberry constituents prevent SOS-mediated filamentation of uropathogenic <i>Escherichia coli</i>.","authors":"Tracy Prinster, Alistair Harrison, Christopher Dick, Dennis J Horvath, Birong Li, Grace Sievers, Revanth Madamsetty, Jingwen Zhang, Kevin M Mason, Christina Khoo, Sheryl S Justice","doi":"10.1128/iai.00600-24","DOIUrl":"10.1128/iai.00600-24","url":null,"abstract":"<p><p>The diameter, length, and shape of bacteria are maintained with such high fidelity that these parameters are classically used as metrics in the distinction of bacterial species. Increasing evidence indicates that bacteria transiently shift their shapes into distinctive morphologies in response to environmental changes. Elongation of bacterial length into a filamentous shape provides unique survival advantages for many bacterial species. Analysis of 42 clinical isolates of uropathogenic <i>Escherichia coli</i> (UPEC) revealed that filamentation to host-derived antimicrobials is a conserved phenotype. Therefore, we hypothesize that filamentation represents a conserved mechanism of pathogenic bacterial persistence that can be targeted for narrow-spectrum, anti-virulence therapies. We demonstrate that cranberries prevent SulA-mediated filamentation of UPEC. Furthermore, we identify multiple fractions of cranberries that retain anti-filamentation properties. These studies provide mechanistic insight into the clinical efficacy of cranberry for patients with recurrent urinary tract infections. Inhibition of filamentation represents a novel approach to promote bacterial pathogen susceptibility to immune and antibiotic-mediated clearance to attenuate disease.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"93 5","pages":"e0060024"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012910","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":"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":"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":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070743/pdf/","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":"OA","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":"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":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070740/pdf/","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":"OA","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":"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":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070757/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Filamentous bacteriophage M13 induces proinflammatory responses in intestinal epithelial cells.","authors":"Ambarish C Varadan, Juris A Grasis","doi":"10.1128/iai.00618-24","DOIUrl":"10.1128/iai.00618-24","url":null,"abstract":"<p><p>Bacteriophages are the dominant members of the human enteric virome and can shape bacterial communities in the gut; however, our understanding of how they directly impact health and disease is limited. Previous studies have shown that specific bacteriophage populations are expanded in patients with Crohn's disease (CD) and ulcerative colitis (UC), suggesting that fluctuations in the enteric virome may contribute to intestinal inflammation. Based on these studies, we hypothesized that a high bacteriophage burden directly induces intestinal epithelial responses. We found that filamentous bacteriophages M13 and Fd induced dose-dependent IL-8 expression in the human intestinal epithelial cell line HT-29 to a greater degree than their lytic counterparts, T4 and ϕX174. We also found that M13, but not Fd, reduced bacterial internalization in HT-29 cells. This led us to investigate the mechanism underlying M13-mediated inhibition of bacterial internalization by examining the antiviral and antimicrobial responses in these cells. M13 upregulated type I and III IFN expressions and augmented short-chain fatty acid (SCFA)-mediated LL-37 expression in HT-29 cells. Taken together, our data establish that filamentous bacteriophages directly affect human intestinal epithelial cells. These results provide new insights into the complex interactions between bacteriophages and the intestinal mucosa, which may underlie disease pathogenesis.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":"93 5","pages":"e0061824"},"PeriodicalIF":2.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968660","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}