Pub Date : 2025-01-17DOI: 10.1016/j.chom.2024.12.017
José L. Fachi, Sarah de Oliveira, Tihana Trsan, Silvia Penati, Susan Gilfillan, Siyan Cao, Pollyana Ribeiro Castro, Mariane Font Fernandes, Krzysztof L. Hyrc, Xiuli Liu, Patrick Fernandes Rodrigues, Bishan Bhattarai, Brian T. Layden, Marco Aurélio R. Vinolo, Marco Colonna
Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to Clostridioides difficile infection (CDI). We find that a low-fiber diet increases MHC-II expression in the colonic epithelium, which, in turn, worsens CDI by promoting the development of pathogenic CD4+ intraepithelial lymphocytes (IELs). The influence of dietary fibers on MHC-II expression is mediated by its metabolic product, acetate, and its receptor, free fatty acid receptor 2 (FFAR2). While acetate activation of FFAR2 on epithelial cells helps resist CDI, it does not directly regulate MHC-II expression. Instead, MHC-II is regulated by FFAR2 in type 3 innate lymphoid cells (ILC3s). Acetate enhances interleukin-22 (IL-22) production by ILC3s, which then suppresses MHC-II expression on the colonic epithelium. In conclusion, a low-fiber diet reduces acetate-induced IL-22 production by ILC3s, leading to increased MHC-II on the colonic epithelium. This change affects recovery from CDI by expanding the population of pathogenic CD4+ IELs.
{"title":"Fiber- and acetate-mediated modulation of MHC-II expression on intestinal epithelium protects from Clostridioides difficile infection","authors":"José L. Fachi, Sarah de Oliveira, Tihana Trsan, Silvia Penati, Susan Gilfillan, Siyan Cao, Pollyana Ribeiro Castro, Mariane Font Fernandes, Krzysztof L. Hyrc, Xiuli Liu, Patrick Fernandes Rodrigues, Bishan Bhattarai, Brian T. Layden, Marco Aurélio R. Vinolo, Marco Colonna","doi":"10.1016/j.chom.2024.12.017","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.017","url":null,"abstract":"Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to <em>Clostridioides difficile</em> infection (CDI). We find that a low-fiber diet increases MHC-II expression in the colonic epithelium, which, in turn, worsens CDI by promoting the development of pathogenic CD4<sup>+</sup> intraepithelial lymphocytes (IELs). The influence of dietary fibers on MHC-II expression is mediated by its metabolic product, acetate, and its receptor, free fatty acid receptor 2 (FFAR2). While acetate activation of FFAR2 on epithelial cells helps resist CDI, it does not directly regulate MHC-II expression. Instead, MHC-II is regulated by FFAR2 in type 3 innate lymphoid cells (ILC3s). Acetate enhances interleukin-22 (IL-22) production by ILC3s, which then suppresses MHC-II expression on the colonic epithelium. In conclusion, a low-fiber diet reduces acetate-induced IL-22 production by ILC3s, leading to increased MHC-II on the colonic epithelium. This change affects recovery from CDI by expanding the population of pathogenic CD4<sup>+</sup> IELs.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"95 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987461","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}
Pub Date : 2025-01-15DOI: 10.1016/j.chom.2024.12.016
Gorka Lasso, Michael Grodus, Estefania Valencia, Veronica DeJesus, Eliza Liang, Isabel Delwel, Rob H. Bortz, Dmitry Lupyan, Hanna Y. Ehrlich, Adrian A. Castellanos, Andrea Gazzo, Heather L. Wells, Supaporn Wacharapluesadee, Alexandre Tremeau-Bravard, Janine F.R. Seetahal, Tom Hughes, Jimmy Lee, Mei-Ho Lee, Anna R. Sjodin, Marike Geldenhuys, Simon J. Anthony
Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species. We found that GP-NPC1 binding correlated poorly with phylogeny. By integrating binding assays with machine learning, we identified genetic factors influencing virus-receptor-binding and predicted GP-NPC1-binding avidity for additional filoviruses and bats. Moreover, combining receptor-binding avidities with bat geographic distribution and the locations of previous Ebola outbreaks allowed us to rank bats by their potential as Ebola virus hosts. This study represents a comprehensive investigation of filovirus-receptor binding in bats (1,484 GP-NPC1 pairs, 11 filoviruses, and 135 bats) and describes a multidisciplinary approach to predict susceptible species and guide filovirus host surveillance.
{"title":"Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning","authors":"Gorka Lasso, Michael Grodus, Estefania Valencia, Veronica DeJesus, Eliza Liang, Isabel Delwel, Rob H. Bortz, Dmitry Lupyan, Hanna Y. Ehrlich, Adrian A. Castellanos, Andrea Gazzo, Heather L. Wells, Supaporn Wacharapluesadee, Alexandre Tremeau-Bravard, Janine F.R. Seetahal, Tom Hughes, Jimmy Lee, Mei-Ho Lee, Anna R. Sjodin, Marike Geldenhuys, Simon J. Anthony","doi":"10.1016/j.chom.2024.12.016","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.016","url":null,"abstract":"Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species. We found that GP-NPC1 binding correlated poorly with phylogeny. By integrating binding assays with machine learning, we identified genetic factors influencing virus-receptor-binding and predicted GP-NPC1-binding avidity for additional filoviruses and bats. Moreover, combining receptor-binding avidities with bat geographic distribution and the locations of previous Ebola outbreaks allowed us to rank bats by their potential as Ebola virus hosts. This study represents a comprehensive investigation of filovirus-receptor binding in bats (1,484 GP-NPC1 pairs, 11 filoviruses, and 135 bats) and describes a multidisciplinary approach to predict susceptible species and guide filovirus host surveillance.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"28 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981358","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}
Enterovirus D68 (EV-D68) is a leading non-polio enterovirus that causes severe respiratory diseases and poliomyelitis-like illness in children. Viral entry represents a potential multifaceted target for antiviral intervention; however, there are no approved inhibitors to block EV-D68. Here, we identify the functionally undescribed membrane protein major facilitator superfamily-domain-containing protein 6 (MFSD6) as an EV-D68 entry factor amenable to therapeutic intervention. Specifically, MFSD6 expression is crucial for EV-D68 replication. MFSD6 binds to EV-D68 particles and is necessary for virus attachment to cells. The second extracellular domain of the MFSD6 molecule is involved in the recognition of EV-D68. On the basis of these findings, we engineered a recombinant protein complex comprising the MFSD6 ectodomain fused to Fc (MFSD6-Fc(CH3)), which potently inhibited EV-D68 uptake. MFSD6-Fc(CH3) effectively blocked EV-D68 infection in vitro and prevented lethality in newborn mice. In conclusion, our study not only identifies MFSD6 as an EV-D68 entry factor but also reveals a potential antiviral target and therapeutic agent.
{"title":"MFSD6 is an entry receptor for respiratory enterovirus D68","authors":"Xize Liu, Huili Li, Zhaoxue Li, Delong Gao, Junfeng Zhou, Fushun Ni, Qing Yu, Yuehan Huang, Yubin Tang, Ling Xue, Shijin Wang, Jiaxin Yang, Haoran Guo, Yonggang Wang, Xiao-Fang Yu, Zhenglei Yu, Wei Wei","doi":"10.1016/j.chom.2024.12.015","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.015","url":null,"abstract":"Enterovirus D68 (EV-D68) is a leading non-polio enterovirus that causes severe respiratory diseases and poliomyelitis-like illness in children. Viral entry represents a potential multifaceted target for antiviral intervention; however, there are no approved inhibitors to block EV-D68. Here, we identify the functionally undescribed membrane protein major facilitator superfamily-domain-containing protein 6 (MFSD6) as an EV-D68 entry factor amenable to therapeutic intervention. Specifically, MFSD6 expression is crucial for EV-D68 replication. MFSD6 binds to EV-D68 particles and is necessary for virus attachment to cells. The second extracellular domain of the MFSD6 molecule is involved in the recognition of EV-D68. On the basis of these findings, we engineered a recombinant protein complex comprising the MFSD6 ectodomain fused to Fc (MFSD6-Fc(CH3)), which potently inhibited EV-D68 uptake. MFSD6-Fc(CH3) effectively blocked EV-D68 infection <em>in vitro</em> and prevented lethality in newborn mice. In conclusion, our study not only identifies MFSD6 as an EV-D68 entry factor but also reveals a potential antiviral target and therapeutic agent.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"28 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939629","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}
Pub Date : 2025-01-08DOI: 10.1016/j.chom.2024.12.014
David A. Baltrus, Brian H. Kvitko
The report from Grenz et al. in the latest issue of Cell Host & Microbe demonstrates how incorporation of phenotypic, genetic, genomic, and evolutionary information into experimental design provides a more complete picture than focusing on single host-pathogen relationships.
{"title":"Exploring the open (host) range","authors":"David A. Baltrus, Brian H. Kvitko","doi":"10.1016/j.chom.2024.12.014","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.014","url":null,"abstract":"The report from Grenz et al. in the latest issue of <em>Cell Host & Microbe</em> demonstrates how incorporation of phenotypic, genetic, genomic, and evolutionary information into experimental design provides a more complete picture than focusing on single host-pathogen relationships.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"8 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936224","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}
Pub Date : 2025-01-08DOI: 10.1016/j.chom.2024.12.006
Jiayu Wu, Kai Wang, Xinyu Qi, Shuang Zhou, Shuyun Zhao, Meisong Lu, Qixing Nie, Meng Li, Mengwei Han, Xi Luo, Chuyu Yun, Pengcheng Wang, Rong Li, Chao Zhong, Xiaofei Yu, Wen-bing Yin, Changtao Jiang, Jie Qiao, Yanli Pang
Polycystic ovary syndrome (PCOS) affects 6%–10% of women of reproductive age and is known to be associated with disruptions in the gut bacteria. However, the role of the gut mycobiota in PCOS pathology remains unclear. Using culture-dependent and internal transcribed spacer 2 (ITS2)-sequencing methods, we discovered an enrichment of the gut-colonizable fungus Aspergillus tubingensis in 226 individuals, with or without PCOS, from 3 different geographical areas within China. Colonization of mice with A. tubingensis led to a PCOS-like phenotype due to inhibition of Aryl hydrocarbon receptor (AhR) signaling and reduced interleukin (IL)-22 secretion in intestinal group 3 innate lymphoid cells (ILC3s). By developing a strain-diversity-based-activity metabolite screening workflow, we identified secondary metabolite AT-C1 as an endogenous AhR antagonist and a key mediator of PCOS. Our findings demonstrate that an intestinal fungus and its secondary metabolite play a critical role in PCOS pathogenesis, offering a therapeutic strategy for improving the management of the disease.
{"title":"The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite","authors":"Jiayu Wu, Kai Wang, Xinyu Qi, Shuang Zhou, Shuyun Zhao, Meisong Lu, Qixing Nie, Meng Li, Mengwei Han, Xi Luo, Chuyu Yun, Pengcheng Wang, Rong Li, Chao Zhong, Xiaofei Yu, Wen-bing Yin, Changtao Jiang, Jie Qiao, Yanli Pang","doi":"10.1016/j.chom.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.006","url":null,"abstract":"Polycystic ovary syndrome (PCOS) affects 6%–10% of women of reproductive age and is known to be associated with disruptions in the gut bacteria. However, the role of the gut mycobiota in PCOS pathology remains unclear. Using culture-dependent and internal transcribed spacer 2 (ITS2)-sequencing methods, we discovered an enrichment of the gut-colonizable fungus <em>Aspergillus tubingensis</em> in 226 individuals, with or without PCOS, from 3 different geographical areas within China. Colonization of mice with <em>A. tubingensis</em> led to a PCOS-like phenotype due to inhibition of Aryl hydrocarbon receptor (AhR) signaling and reduced interleukin (IL)-22 secretion in intestinal group 3 innate lymphoid cells (ILC3s). By developing a strain-diversity-based-activity metabolite screening workflow, we identified secondary metabolite AT-C1 as an endogenous AhR antagonist and a key mediator of PCOS. Our findings demonstrate that an intestinal fungus and its secondary metabolite play a critical role in PCOS pathogenesis, offering a therapeutic strategy for improving the management of the disease.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"35 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936084","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}
Pub Date : 2025-01-08DOI: 10.1016/j.chom.2024.12.005
Tian-Yi Zhang, Ning-Ning Liu
In this issue of Cell Host & Microbe, Wu et al. identified enriched gut Aspergillus tubingensis in patients with polycystic ovary syndrome (PCOS). In mice, this fungus induced a PCOS-like phenotype by inhibiting interleukin (IL)-22 secretion from ILC3s via the AT-C1-AhR axis. PCOS, a women’s health concern, is influenced by the gut mycobiome.
{"title":"Fungal influence: The role of the gut mycobiome in women’s health","authors":"Tian-Yi Zhang, Ning-Ning Liu","doi":"10.1016/j.chom.2024.12.005","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.005","url":null,"abstract":"In this issue of <em>Cell Host & Microbe</em>, Wu et al. identified enriched gut <em>Aspergillus tubingensis</em> in patients with polycystic ovary syndrome (PCOS). In mice, this fungus induced a PCOS-like phenotype by inhibiting interleukin (IL)-22 secretion from ILC3s via the AT-C1-AhR axis. PCOS, a women’s health concern, is influenced by the gut mycobiome.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"8 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936082","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}
Pub Date : 2025-01-08DOI: 10.1016/j.chom.2024.12.012
Dingjiacheng Jia, Shujie Chen
Fungal symbionts play a key role in maintaining host homeostasis. In a recent issue of Nature, Liao et al. show that Kazachstania pintolopesii, a symbiotic fungus in mice, is shielded from the host immune system during homeostasis but induces type 2 immunity during mucus fluctuations.
{"title":"Commensal fungi, a force to be reckoned with","authors":"Dingjiacheng Jia, Shujie Chen","doi":"10.1016/j.chom.2024.12.012","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.012","url":null,"abstract":"Fungal symbionts play a key role in maintaining host homeostasis. In a recent issue of <em>Nature</em>, Liao et al. show that <em>Kazachstania pintolopesii</em>, a symbiotic fungus in mice, is shielded from the host immune system during homeostasis but induces type 2 immunity during mucus fluctuations.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"77 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936083","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}
Pub Date : 2025-01-08DOI: 10.1016/j.chom.2024.12.010
Weihong Wang, Zheshun Pi, You Yu, Faming Zhang
Strain-level variation in the gut microbiome modulates its impact on host health. Recently in Nature, Chen-Liaw et al. propose that strain richness is a crucial element in the gut ecosystem, thus influencing efficacy of fecal microbiota transplantation, and provide a theoretical foundation for optimizing microbiota-based treatments and developing microbiota medicine.
{"title":"The butterfly effect of the strain richness influences the efficacy of microbiota transplantation","authors":"Weihong Wang, Zheshun Pi, You Yu, Faming Zhang","doi":"10.1016/j.chom.2024.12.010","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.010","url":null,"abstract":"Strain-level variation in the gut microbiome modulates its impact on host health. Recently in <em>Nature</em>, Chen-Liaw et al. propose that strain richness is a crucial element in the gut ecosystem, thus influencing efficacy of fecal microbiota transplantation, and provide a theoretical foundation for optimizing microbiota-based treatments and developing microbiota medicine.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"19 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936188","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}
Pub Date : 2025-01-08DOI: 10.1016/j.chom.2024.12.013
Jinzhong Lin, Yuvaraj Bhoobalan-Chitty, Xu Peng
Type III CRISPR-Cas executes a multifaceted anti-phage response, activating effectors such as a nuclease or membrane depolarizer. In a recent Cell paper, Baca and Majumder et al.1 report an accessory effector, Cad1, which deaminates ATP into ITP, causing ITP accumulation and host growth arrest, thereby inhibiting phage propagation.
{"title":"Cad1 turns ATP into phage poison","authors":"Jinzhong Lin, Yuvaraj Bhoobalan-Chitty, Xu Peng","doi":"10.1016/j.chom.2024.12.013","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.013","url":null,"abstract":"Type III CRISPR-Cas executes a multifaceted anti-phage response, activating effectors such as a nuclease or membrane depolarizer. In a recent <em>Cell</em> paper, Baca and Majumder et al.<span><span><sup>1</sup></span></span> report an accessory effector, Cad1, which deaminates ATP into ITP, causing ITP accumulation and host growth arrest, thereby inhibiting phage propagation.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"99 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936078","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}
Pub Date : 2025-01-08DOI: 10.1016/j.chom.2024.12.009
Tyson R. Chiaro, Morgan Greenewood, Kaylyn M. Bauer, Kyla S. Ost, Emmanuel Stephen-Victor, Michaela Murphy, Allison M. Weis, Morgan C. Nelson, Jennifer H. Hill, Rickesha Bell, Warren Voth, Taylor Jackson, Kendra A. Klag, Ryan M. O’Connell, W. Zac Stephens, June L. Round
Microbiota composition regulates colitis severity, yet the innate immune mechanisms that control commensal communities and prevent disease remain unclear. We show that the innate immune receptor, Clec12a, impacts colitis severity by regulating microbiota composition. Transplantation of microbiota from a Clec12a−/− animal is sufficient to worsen colitis in wild-type mice. Clec12a−/− mice have expanded Faecalibaculum rodentium, and treatment with F. rodentium similarly exacerbates disease. However, Clec12a−/− animals are resistant to colitis development when rederived into an 11-member community, underscoring the role of specific species. Colitis in Clec12a−/− mice is dependent on monocytes, and cytokine and sequencing analysis in Clec12a−/− macrophages and serum shows enhanced inflammation with a reduction in phagocytic genes. F. rodentium specifically binds to Clec12a, and Clec12a−/−-deficient macrophages are impaired in their ability to phagocytose F. rodentium. Thus, Clec12a contributes to an innate-immune-surveillance mechanism that controls the expansion of potentially harmful commensals while limiting inflammation.
{"title":"Clec12a controls colitis by tempering inflammation and restricting expansion of specific commensals","authors":"Tyson R. Chiaro, Morgan Greenewood, Kaylyn M. Bauer, Kyla S. Ost, Emmanuel Stephen-Victor, Michaela Murphy, Allison M. Weis, Morgan C. Nelson, Jennifer H. Hill, Rickesha Bell, Warren Voth, Taylor Jackson, Kendra A. Klag, Ryan M. O’Connell, W. Zac Stephens, June L. Round","doi":"10.1016/j.chom.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.009","url":null,"abstract":"Microbiota composition regulates colitis severity, yet the innate immune mechanisms that control commensal communities and prevent disease remain unclear. We show that the innate immune receptor, Clec12a, impacts colitis severity by regulating microbiota composition. Transplantation of microbiota from a Clec12a<sup>−/−</sup> animal is sufficient to worsen colitis in wild-type mice. Clec12a<sup>−/−</sup> mice have expanded <em>Faecalibaculum rodentium</em>, and treatment with <em>F. rodentium</em> similarly exacerbates disease. However, Clec12a<sup>−/−</sup> animals are resistant to colitis development when rederived into an 11-member community, underscoring the role of specific species. Colitis in Clec12a<sup>−/−</sup> mice is dependent on monocytes, and cytokine and sequencing analysis in Clec12a<sup>−/−</sup> macrophages and serum shows enhanced inflammation with a reduction in phagocytic genes. <em>F. rodentium</em> specifically binds to Clec12a, and Clec12a<sup>−/−</sup>-deficient macrophages are impaired in their ability to phagocytose <em>F. rodentium</em>. Thus, Clec12a contributes to an innate-immune-surveillance mechanism that controls the expansion of potentially harmful commensals while limiting inflammation.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"30 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936085","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}
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