Microbes and Infection最新文献_第6页

Machine learning-based characterization of the gut microbiome associated with the progression of primary biliary cholangitis to cirrhosis 基于机器学习的与原发性胆汁性胆管炎发展为肝硬化相关的肠道微生物组特征描述

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105368

Qi Wang , Xiaomeng Tang , Wenying Qiao , Lina Sun , Han Shi , Dexi Chen , Bin Xu , Yanmin Liu , Juan Zhao , Chunyang Huang , Ronghua Jin

{"title":"Machine learning-based characterization of the gut microbiome associated with the progression of primary biliary cholangitis to cirrhosis","authors":"Qi Wang , Xiaomeng Tang , Wenying Qiao , Lina Sun , Han Shi , Dexi Chen , Bin Xu , Yanmin Liu , Juan Zhao , Chunyang Huang , Ronghua Jin","doi":"10.1016/j.micinf.2024.105368","DOIUrl":"10.1016/j.micinf.2024.105368","url":null,"abstract":"<div><h3>Background</h3><div><span>Primary biliary cholangitis (PBC) is associated closely with the </span>gut microbiota<span><span>. This study aimed to explore the characteristics of the gut microbiota after the progress of PBC to </span>cirrhosis.</span></div></div><div><h3>Method</h3><div>This study focuses on utilizing the 16S rRNA<span> gene sequencing method to screen for differences in gut microbiota<span> in PBC patients who progress to cirrhosis. Then, we divided the data into training and verification sets and used seven different machine learning (ML) models to validate them respectively, calculating and comparing the accuracy, F1 score, precision, and recall, and screening the dominant intestinal flora affecting PBC cirrhosis.</span></span></div></div><div><h3>Result</h3><div><span>PBC cirrhosis patients showed decreased diversity and richness of gut microbiota. Additionally, there are alterations in the composition of gut microbiota in PBC cirrhosis patients. The abundance of </span><span><span>Faecalibacterium</span></span> and <em>Gemmiger</em> bacteria significantly decreases, while the abundance of <span><span>Veillonella</span></span> and <span><span>Streptococcus</span></span> significantly increases. Furthermore, machine learning methods identify <span><span>Streptococcus</span></span> and <em>Gemmiger</em> as the predominant gut microbiota in PBC patients with cirrhosis, serving as non-invasive biomarkers (AUC = 0.902).</div></div><div><h3>Conclusion</h3><div>Our study revealed that PBC cirrhosis patients gut microbiota composition and function have significantly changed. <em>Streptococcus</em> and <em>Gemmiger</em> may become a non-invasive biomarker for predicting the progression of PBC progress to cirrhosis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105368"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141137069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of cilia in chemosensory neurons inhibits pathogen avoidance in Caenorhabditis elegans 化感神经元中纤毛的缺失会抑制秀丽隐杆线虫的病原体规避能力

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105370

Ming Lei , Yanheng Tan , Jingyi Ke , Mengqi Wang , Zeyang He , Guangshuo Ou , Haijun Tu , Weihong Tan

{"title":"Loss of cilia in chemosensory neurons inhibits pathogen avoidance in Caenorhabditis elegans","authors":"Ming Lei , Yanheng Tan , Jingyi Ke , Mengqi Wang , Zeyang He , Guangshuo Ou , Haijun Tu , Weihong Tan","doi":"10.1016/j.micinf.2024.105370","DOIUrl":"10.1016/j.micinf.2024.105370","url":null,"abstract":"<div><div>Pathogen avoidance is a crucial and evolutionarily conserved behavior that enhances survival by preventing infection in diverse species, including <span><span>Caenorhabditis elegans</span></span> (<em>C. elegans</em>). This behavior relies on multiple chemosensory neurons equipped with cilia that are exposed to the external environment. However, the specific role of neuronal cilia in pathogen avoidance has not been completely elucidated. Herein, we discovered that <em>osm-3(p802)</em> mutants, which lack chemosensory neuronal cilia, exhibit slower avoidance of the pathogen <span><span>Pseudomonas aeruginosa</span></span><span> PA14, but not </span><em>Escherichia coli</em> OP50. This observation was consistent when <em>osm-3(p802)</em> mutants were exposed to <em>P. aeruginosa</em><span> PAO1. Following an encounter with PA14, the pumping, thrashing, and defecation behaviors of </span><em>osm-3</em> mutants were comparable to those of the wild-type. However, the <em>osm-3</em><span> mutants demonstrated reduced intestinal colonization of PA14, suggesting that they have stronger intestinal clearance ability. We conducted RNA-seq to identify genes responding to external stimuli that were differentially expressed owing to the loss of </span><em>osm-3</em><span> and PA14 infection. Using RNAi, we demonstrated that three of these genes were essential for normal pathogen avoidance. In conclusion, our findings demonstrate that the loss of chemosensory neuronal cilia reduces pathogen avoidance in </span><em>C. elegans</em> while delaying intestinal colonization.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105370"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pertussis toxin-dependent and -independent protection by Bordetella pertussis against influenza 百日咳杆菌对流感的百日咳毒素依赖性和非依赖性保护。

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105404

Thomas Belcher , Loïc Coutte , Anne-Sophie Debrie, Valentin Sencio, François Trottein, Camille Locht , Stephane Cauchi

{"title":"Pertussis toxin-dependent and -independent protection by Bordetella pertussis against influenza","authors":"Thomas Belcher , Loïc Coutte , Anne-Sophie Debrie, Valentin Sencio, François Trottein, Camille Locht , Stephane Cauchi","doi":"10.1016/j.micinf.2024.105404","DOIUrl":"10.1016/j.micinf.2024.105404","url":null,"abstract":"<div><div>Bacterial-viral co-infections are frequent, but their reciprocal effects are not well understood. Here, we examined the effect <em>Bordetella pertussis</em> infection and the role of pertussis toxin (PT) on influenza A virus (IAV) infection and disease. In C57BL/6J mice, prior nasal administration of virulent <em>B. pertussis</em> BPSM and PT-deficient BPRA provided effective and sustained protection from IAV-induced mortality. However, BPSM or BPRA administered together with purified PT (BPRA + PT) had a stronger protective effect on weight loss compared to BPRA alone, reduced the viral load, and induced IL-17A in the lungs. In IL-17<sup>−/−</sup> mice, BPSM- and BPRA + PT-mediated protection against viral replication was abolished, while BPSM, BPRA and BPRA + PT provided similar levels of protection against IAV-induced mortality and weight loss. In conclusion, <em>B. pertussis</em> infection protects against influenza by two mechanisms: one reducing viral replication depending on PT and IL-17, and the other, independently of PT and IL-17, resulting in protection against influenza disease without reducing the viral load.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105404"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung infection with classical Klebsiella pneumoniae strains establishes robust macrophage-dependent protection against heterologous reinfection 经典肺炎克雷伯氏菌菌株的肺部感染可建立对异源再感染的强大巨噬细胞依赖性保护。

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105369

Joseph J. Mackel , Casey L.G. Mick , Emily Guo , David A. Rosen

{"title":"Lung infection with classical Klebsiella pneumoniae strains establishes robust macrophage-dependent protection against heterologous reinfection","authors":"Joseph J. Mackel , Casey L.G. Mick , Emily Guo , David A. Rosen","doi":"10.1016/j.micinf.2024.105369","DOIUrl":"10.1016/j.micinf.2024.105369","url":null,"abstract":"<div><div>At present, there is no approved vaccine for prevention of infection by the opportunistic bacterium <em>Klebsiella pneumoniae</em> (Kp); success in treating these infections is increasingly challenged by the spread of antibiotic resistance. Preclinical investigation of adaptive immunity elicited by lung infection with live classical Kp may reveal host mechanisms of protection against this pathogen. Here, we utilize multiple virulent classical Kp strains to demonstrate that following lung infection, surviving wild-type mice develop protective immunity against both homologous and heterologous (heterotypic) reinfection. For Kp strains with low capacity to disseminate from the lung, this immunity is B-cell-independent. We further demonstrate that this immune protection is also effective against subsequent challenge with hypervirulent Kp if the strains share the same capsule type. Systemic inoculation fails to elicit the same protective effect as lung inoculation, revealing a lung-specific immune effector function is responsible for this protection. We therefore utilized clodronate-loaded liposomes to substantially deplete both alveolar macrophages and lung interstitial macrophages, finding that simultaneous depletion of both subsets entirely ablates protection. These findings indicate that following initial lung infection with Kp, lung macrophages mediate protection against ensuing Kp challenge.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105369"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179972","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}

引用次数: 0

Efficacy of macozinone in mice with genetically diverse susceptibility to Mycobacterium tuberculosis infection 麦考嗪酮对不同基因的结核分枝杆菌感染小鼠的疗效

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105376

Boris Nikonenko , Nadezhda Logunova , Anna Egorova , Marina Kapina , Natalia Sterzhanova , Irina Bocharova , Elena Kondratieva , Olga Riabova , Lyudmila Semyonova , Vadim Makarov , Dedicated to the 10th anniversary of the iM4TB Foundation

{"title":"Efficacy of macozinone in mice with genetically diverse susceptibility to Mycobacterium tuberculosis infection","authors":"Boris Nikonenko , Nadezhda Logunova , Anna Egorova , Marina Kapina , Natalia Sterzhanova , Irina Bocharova , Elena Kondratieva , Olga Riabova , Lyudmila Semyonova , Vadim Makarov , Dedicated to the 10th anniversary of the iM4TB Foundation","doi":"10.1016/j.micinf.2024.105376","DOIUrl":"10.1016/j.micinf.2024.105376","url":null,"abstract":"<div><div><span>Host heterogeneity in pulmonary tuberculosis<span> leads to varied responses to infection and drug treatment. The present portfolio of anti-TB drugs needs to be boosted with new drugs and drug regimens. Macozinone, a clinical-stage molecule targeting the essential enzyme, DprE1, represents an attractive option. Mice (I/St, B6, (AKRxI/St)F1, B6.I-100 and B6.I-139) genetically diverse susceptibility to </span></span><span><em>Mycobacterium tuberculosis</em></span> (<em>Mtb</em>) H37Rv infection were subjected to aerosol- or intravenous infection to determine the efficacy of macozinone (MCZ). They were treated with macozinone or reference drugs (isoniazid, rifampicin). Lung and spleen bacterial burdens were measured at four and eight weeks post-infection. Lung histology was evaluated at four weeks of treatment. Treatment with macozinone resulted in a statistically significant reduction in the bacterial load in the lungs and spleen as early as four weeks after treatment initiation in mice susceptible or resistant to <em>Mtb</em><span> infection. In the TB hypoxic granuloma<span> model, macozinone was more potent than rifampicin in reducing the CFU counts. However, histopathological analysis revealed significant lung changes in I/St mice after eight weeks of treatment initiation. Macozinone demonstrated efficacy to varying degrees across all mouse models of </span></span><em>Mtb</em> infection used. These results should facilitate its further development and potential introduction into clinical practice.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105376"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Staphylococcus pseudintermedius and Pseudomonas aeruginosa Lubbock Chronic Wound Biofilm (LCWB): a suitable dual-species model for in vitro studies 假中间葡萄球菌和铜绿假单胞菌卢伯克慢性伤口生物膜（LCWB）：体外研究的合适双菌种模型。

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105384

Silvia Di Lodovico , Morena Petrini , Paola Di Fermo , Valeria De Pasquale , Luisa De Martino , Simonetta D'Ercole , Francesca Paola Nocera , Mara Di Giulio

{"title":"Staphylococcus pseudintermedius and Pseudomonas aeruginosa Lubbock Chronic Wound Biofilm (LCWB): a suitable dual-species model for in vitro studies","authors":"Silvia Di Lodovico , Morena Petrini , Paola Di Fermo , Valeria De Pasquale , Luisa De Martino , Simonetta D'Ercole , Francesca Paola Nocera , Mara Di Giulio","doi":"10.1016/j.micinf.2024.105384","DOIUrl":"10.1016/j.micinf.2024.105384","url":null,"abstract":"<div><div>Antimicrobial treatment of methicillin-resistant <em>Staphylococcus pseudintermedius</em> associated with canine wounds represents an important challenge. The aim of this study was to create a canine wound infection model, Lubbock Chronic Wound Biofilm (LCWB), with a focus on <em>S. pseudintermedius,</em> drawing inspiration from the established human model involving <em>Staphylococcus aureus</em>. Methicillin-resistant <em>S. pseudintermedius</em> 115 (MRSP) and <em>Pseudomonas aeruginosa</em> 700 strains, isolated from dog wounds, were used to set up the LCWB at 24, 48 and 72 h. The LCWBs were evaluated in terms of volume, weight, and microbial CFU/mg. The microbial spatial distribution in the LCWBs was assessed by SEM and CLSM imaging. The best incubation time for the LCWB production in terms of volume (3.38 cm<sup>3</sup> ± 0.13), weight (0.86 gr ± 0.02) and CFU/mg (up to 7.05 × 10<sup>6</sup> CFU/mg ± 2.89 × 10<sup>5</sup>) was 48 h. The SEM and CLSM images showed a major viable microbial colonization at 48 h with non-mixed bacteria with a prevalence of MRSP on the surface and <em>P. aeruginosa</em> 700 in the depth of the wound. The obtained findings demonstrate the capability of <em>S. pseudintermedius</em> to grow together <em>P. aeruginosa</em> in the LCWB model, representing the suitable model to reproduce the animal chronic wound <em>in vitro</em>.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105384"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469341","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}

引用次数: 0

Host-specific SRSF7 regulates polymerase activity and replication of influenza A virus 宿主特异性 SRSF7 可调节甲型流感病毒的聚合酶活性和复制。

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105401

Lingcai Zhao , Shengmin Li , Lulu Deng , Yijia Zhang , Chenfeng Jiang , Yurong Wei , Jun Xia , Jihui Ping

{"title":"Host-specific SRSF7 regulates polymerase activity and replication of influenza A virus","authors":"Lingcai Zhao , Shengmin Li , Lulu Deng , Yijia Zhang , Chenfeng Jiang , Yurong Wei , Jun Xia , Jihui Ping","doi":"10.1016/j.micinf.2024.105401","DOIUrl":"10.1016/j.micinf.2024.105401","url":null,"abstract":"<div><div>Avian influenza viruses crossing the host barrier to infect humans have caused great panic in human society and seriously threatened public health. Herein, we revealed that knockdown of SRSF7 significantly down-regulated influenza virus titers and viral protein expression. We further observed for the first time that human SRSF7, but not avian SRSF7, significantly inhibited polymerase activity (PB2<sub>627</sub>E). Molecular mapping demonstrated that amino acids 206 to 228 of human SRSF7 play a decisive role in regulating the polymerase activity, which contains the amino acid motif absent in avian SRSF7. Importantly, our results illustrated that the PB2<sub>627</sub>K-encoding influenza virus induces SRSF7 protein degradation more strongly via the lysosome pathway and not via the proteasome pathway. Functional enrichment analysis of SRSF7-related KEGG pathways indicated that SRSF7 is closely related to cell growth and death. Lastly, our results showed that knocking down SRSF7 interferes with normal polymerase activity. Taken together, our results advance our understanding of interspecies transmission and our findings point out new targets for the development of drugs preventing or treating influenza virus infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105401"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971466","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}

引用次数: 0

Extracellular vesicles in the pathogenesis of Campylobacter jejuni 空肠弯曲杆菌致病过程中的胞外囊泡。

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105377

Jeanne Malet-Villemagne, Jasmina Vidic

引用次数: 0

The PDZ domain of the E protein in SARS-CoV induces carcinogenesis and poor prognosis in LUAD SARS-CoV中E蛋白的PDZ域诱导LUAD的癌变和不良预后

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105381

Shun Li , Jinxuan Wang , Xiaozhen Dai , Churong Li , Tao Li , Long Chen

{"title":"The PDZ domain of the E protein in SARS-CoV induces carcinogenesis and poor prognosis in LUAD","authors":"Shun Li , Jinxuan Wang , Xiaozhen Dai , Churong Li , Tao Li , Long Chen","doi":"10.1016/j.micinf.2024.105381","DOIUrl":"10.1016/j.micinf.2024.105381","url":null,"abstract":"<div><h3>Background</h3><div><span>In both lung adenocarcinoma (LUAD) and </span>severe acute respiratory syndrome<span><span> (SARS), uncontrolled inflammation can be detected in lung tissue. The PDZ-binding motif (PBM) in the SARS-CoV-1 E protein has been demonstrated to be a virulence factor that induces a </span>cytokine storm.</span></div></div><div><h3>Methods</h3><div><span>To identify gene expression fluctuations induced by PBM, microarray sequencing data of lung tissue infected with wild-type (SARS-CoV-1-E-wt) or </span>recombinant virus<span> (SARS-CoV-1-E-mutPBM) were analyzed, followed by functional enrichment analysis. To understand the role of the screened genes in LUAD, overall survival and immune correlation were calculated.</span></div></div><div><h3>Results</h3><div><span>A total of 12 genes might participate in the initial and developmental stages of LUAD through expression variation and mutation. Moreover, dysregulation of a total of 12 genes could lead to a poorer prognosis. In addition, the downregulation<span> of MAMDC2 and ITGA8 by PBM could also affect patient prognosis. Although the conserved PBM (-D-L-L-V-) can be found at the end of the carboxyl terminus in multiple E proteins of </span></span>coronaviruses<span>, the specific function of each protein depends on the entire amino acid sequence.</span></div></div><div><h3>Conclusions</h3><div>In summary, PBM containing the SARS-CoV-1 E protein promoted the carcinogenesis of LUAD by dysregulating important gene expression profiles and subsequently influencing the immune response and overall prognosis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105381"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NLRP1B allele 2 does not respond to Val-boro-Pro (VbP) in intestinal epithelial cells 肠上皮细胞中表达的 NLRP1B 对 Val-boro-Pro 的激活具有耐受性。

IF 2.6 4区医学

Microbes and Infection Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105398

Ryan J. Mazzone , Nathaniel J. Winsor , Lu Yi Li , Kristian T. Barry , Adrienne Ranger , Shawn Goyal , Justin J. Meade , Jessica Bruce , Dana J. Philpott , Jeremy Mogridge , Stephen E. Girardin

{"title":"NLRP1B allele 2 does not respond to Val-boro-Pro (VbP) in intestinal epithelial cells","authors":"Ryan J. Mazzone , Nathaniel J. Winsor , Lu Yi Li , Kristian T. Barry , Adrienne Ranger , Shawn Goyal , Justin J. Meade , Jessica Bruce , Dana J. Philpott , Jeremy Mogridge , Stephen E. Girardin","doi":"10.1016/j.micinf.2024.105398","DOIUrl":"10.1016/j.micinf.2024.105398","url":null,"abstract":"<div><div>The intestinal mucosa must balance tolerance to commensal microbes and luminal antigens with rapid detection of enteric pathogens in order to maintain homeostasis. This balance is facilitated through the regulation of epithelial layer integrity by innate immune receptors. Certain NOD-like receptors (NLRs) expressed in intestinal epithelial cells, including NLRC4 and NLRP9B, form inflammasomes that protect against pathogens by activating caspase-1 to cause extrusion of infected cells. NLRP1B is a murine NLR encoded by five alleles of a highly polymorphic gene homologous to human NLRP1. NLRP1B forms inflammasomes in response to a variety of pathogens that cause intestinal infections, but it has almost exclusively been studied in immune cells and has not been characterized in cells of the intestinal epithelium. Here, we show that <em>Nlrp1b</em> allele 2 is expressed in ileal and colonic organoids derived for C57BL/6J mice, while the related gene <em>Nlrp1a</em> was not expressed. <em>Nlrp1b</em> was upregulated by interleukin-13 in organoids and by the protozoan <em>Tritrichomonas muris</em> in vivo, suggesting that NLRP1B may be involved in defense against enteric parasites. Surprisingly, while Val-boro-Pro (VbP) activated C57BL/6J-derived bone marrow-derived macrophages, which expressed both <em>Nlrp1a</em> and <em>Nlrp1b</em>, it did not activate intestinal organoids of the same genotype. We furthermore did not detect <em>Nlrp1b</em> in organoids derived from Balb/cJ mice, which express a different allele than the one expressed in C57BL/6J mice. Together, our results suggest that NLRP1B may have an allele-dependent function in murine IECs whose regulation is distinct from that of macrophages, and that the response to VbP might be exclusively driven by NLRP1A in C57BL/6J mice.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105398"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0