Cell host & microbe最新文献

Immunoglobulin A controls intestinal virus colonization to preserve immune homeostasis

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-03-27 DOI: 10.1016/j.chom.2025.03.004

Wioletta Lisicka, Zachary M. Earley, Joseph J. Sifakis, Steven A. Erickson, Jonathan R. Mattingly, Natalie J. Wu-Woods, Siddharth R. Krishnamurthy, Yasmine Belkaid, Rustem F. Ismagilov, Jason G. Cyster, Samantha J. Riesenfeld, Albert Bendelac, Bana Jabri

{"title":"Immunoglobulin A controls intestinal virus colonization to preserve immune homeostasis","authors":"Wioletta Lisicka, Zachary M. Earley, Joseph J. Sifakis, Steven A. Erickson, Jonathan R. Mattingly, Natalie J. Wu-Woods, Siddharth R. Krishnamurthy, Yasmine Belkaid, Rustem F. Ismagilov, Jason G. Cyster, Samantha J. Riesenfeld, Albert Bendelac, Bana Jabri","doi":"10.1016/j.chom.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.004","url":null,"abstract":"Immunoglobulin A (IgA) is the predominant immunoglobulin isotype in mammals, primarily secreted at type I mucosal surfaces. Despite its abundance, the precise role of secretory IgA in the intestinal lumen, where it coats a diverse array of commensal microbiota, has remained elusive. Our study reveals that germinal center IgA responses are essential for preventing chronic colonization of the gut by specific viruses. In the absence of IgA, chronic viral colonization triggers an antigen-driven expansion of CD8αβ+ intraepithelial lymphocytes (IELs). Although these IELs are unable to clear the virus, they contribute to maintaining homeostasis by regulating its load and type I interferon responses. Consequently, IgA deficiency increases susceptibility to colitis in genetically susceptible hosts or following chemical induction but only in the presence of viral pathobionts requiring IgA for their clearance. These findings underscore the potential vulnerability of IgA-deficient individuals to immunopathology when exposed to selective viral pathobionts.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"72 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

A thiouracil desulfurase protects Clostridioides difficile RNA from 4-thiouracil incorporation, providing a competitive advantage in the gut

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-03-25 DOI: 10.1016/j.chom.2025.03.001

Matthew J. Munneke, Yifeng Yuan, Eva C. Preisner, Catherine D. Shelton, Darian T. Carroll, Nicole S. Kirchoff, Ken P. Dickson, Jose O. Cantu, Martin V. Douglass, M. Wade Calcutt, Katherine N. Gibson-Corley, Maribeth R. Nicholson, Mariana X. Byndloss, Robert A. Britton, Valérie de Crécy-Lagard, Eric P. Skaar

{"title":"A thiouracil desulfurase protects Clostridioides difficile RNA from 4-thiouracil incorporation, providing a competitive advantage in the gut","authors":"Matthew J. Munneke, Yifeng Yuan, Eva C. Preisner, Catherine D. Shelton, Darian T. Carroll, Nicole S. Kirchoff, Ken P. Dickson, Jose O. Cantu, Martin V. Douglass, M. Wade Calcutt, Katherine N. Gibson-Corley, Maribeth R. Nicholson, Mariana X. Byndloss, Robert A. Britton, Valérie de Crécy-Lagard, Eric P. Skaar","doi":"10.1016/j.chom.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.chom.2025.03.001","url":null,"abstract":"Nucleotides are essential building blocks for major cellular macromolecules and are critical for life. Consequently, bacterial pathogens must acquire or synthesize nucleotides during infection. Clostridioides difficile is the most common hospital-acquired gastrointestinal infection, and nutrient acquisition is critical for pathogenesis. However, the impact of nucleotide metabolism on C. difficile infection remains unclear. Here, we discover that 4-thiouracil (4-TU), a pyrimidine analog present in the human gut, is toxic to commensal bacteria. 4-TU hijacks the uracil salvage pathway for incorporation into RNA through the uracil phosphoribosyltransferase activity encoded by PyrR and Upp. C. difficile can salvage 4-TU as a pyrimidine source through the enzymatic action of a thiouracil desulfurase (TudS), thereby contributing to C. difficile fitness in mice fed 4-TU or MiniBioreactor models of infection containing exogenous 4-TU. Collectively, these results reveal a molecular mechanism for C. difficile to utilize a poisonous pyrimidine analog in the vertebrate gut to outcompete commensal microbes.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"97 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

RNA editing of genomic neighbors controls antiviral response in fungi

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-03-24 DOI: 10.1016/j.chom.2025.02.016

Shinji Honda, Ayumi Yokoyama, Nobuhiro Suzuki

引用次数: 0

Transcriptional repressor Capicua is a gatekeeper of cell-intrinsic interferon responses

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-03-24 DOI: 10.1016/j.chom.2025.02.017

Senthamizharasi Manivasagam, Julianna Han, Athmane Teghanemt, Henry Keen, Boopathi Sownthirarajan, Boyang Cheng, Abhiraj Singh, Abigail Lewis, Olivia A. Vogel, Gayathri Loganathan, Lei Huang, Maryline Panis, David K. Meyerholz, Benjamin tenOever, Jasmine T. Perez, Santhakumar Manicassamy, Priya D. Issuree, Balaji Manicassamy

{"title":"Transcriptional repressor Capicua is a gatekeeper of cell-intrinsic interferon responses","authors":"Senthamizharasi Manivasagam, Julianna Han, Athmane Teghanemt, Henry Keen, Boopathi Sownthirarajan, Boyang Cheng, Abhiraj Singh, Abigail Lewis, Olivia A. Vogel, Gayathri Loganathan, Lei Huang, Maryline Panis, David K. Meyerholz, Benjamin tenOever, Jasmine T. Perez, Santhakumar Manicassamy, Priya D. Issuree, Balaji Manicassamy","doi":"10.1016/j.chom.2025.02.017","DOIUrl":"https://doi.org/10.1016/j.chom.2025.02.017","url":null,"abstract":"Early detection of viral infection and rapid activation of host antiviral defenses through transcriptional upregulation of interferons (IFNs) and IFN-stimulated genes (ISGs) are critical for controlling infection. However, aberrant production of IFN in the absence of viral infection leads to auto-inflammation and can be detrimental to the host. Here, we show that the DNA-binding transcriptional repressor complex composed of Capicua (CIC) and Ataxin-1 like (ATXN1L) binds to an 8-nucleotide motif near IFN and ISG promoters and prevents erroneous expression of inflammatory genes under homeostasis in humans and mice. By contrast, during respiratory viral infection, activation of the mitogen-activated protein kinase (MAPK) pathway results in rapid degradation of the CIC-ATXN1L complex, thereby relieving repression and allowing for robust induction of IFN and ISGs. Together, our studies define a new paradigm for host regulation of IFN and ISGs through the evolutionarily conserved CIC-ATXN1L transcriptional repressor complex during homeostasis and viral infection.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"94 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

METs, NETs, and UTIs

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-03-12 DOI: 10.1016/j.chom.2025.02.014

Thomas J. Hannan

引用次数: 0

The African gut microbiome: A window into the hidden human microbial diversity

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-03-12 DOI: 10.1016/j.chom.2025.02.015

Shuqin Zeng, Hua Wang, Dezhi Mu, Shaopu Wang

引用次数: 0

It takes three: A cocktail of protists, bacterial sphingolipids and an inflammasome