Pub Date : 2024-09-11DOI: 10.1016/j.chom.2024.08.001
Joshua J. Baty, Julie K. Pfeiffer
Breastfeeding provides infection protection for several pathogens but not for noroviruses. Mechanisms explaining this discrepancy have been unclear. In this issue of Cell Host & Microbe, Peiper et al. demonstrate that while breastmilk protects mice from intestinal damage, it promotes neonatal murine norovirus infection due to maternal-derived bile acids.1
{"title":"Got bile? Breastmilk bile acids influence norovirus infection","authors":"Joshua J. Baty, Julie K. Pfeiffer","doi":"10.1016/j.chom.2024.08.001","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.001","url":null,"abstract":"<p>Breastfeeding provides infection protection for several pathogens but not for noroviruses. Mechanisms explaining this discrepancy have been unclear. In this issue of <em>Cell Host & Microbe</em>, Peiper et al. demonstrate that while breastmilk protects mice from intestinal damage, it promotes neonatal murine norovirus infection due to maternal-derived bile acids.<span><span><sup>1</sup></span></span></p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"10 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166295","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 : 2024-09-11DOI: 10.1016/j.chom.2024.08.005
Yebo Gu, Xin-Ming Jia
During opportunistic pathogenic episodes, Candida albicans employs classical strategies such as the yeast-to-hyphae transition and immunogenic masking. In this issue of Cell Host & Microbe, Luo et al. unveil that the effector protein Cmi1 can be translocated into host cells and targets TBK1, thereby negatively regulating the host’s antifungal immune responses.
{"title":"Stealth strategies of Candida albicans to evade host immunity","authors":"Yebo Gu, Xin-Ming Jia","doi":"10.1016/j.chom.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.005","url":null,"abstract":"<p>During opportunistic pathogenic episodes, <em>Candida albicans</em> employs classical strategies such as the yeast-to-hyphae transition and immunogenic masking. In this issue of <em>Cell Host & Microbe</em>, Luo et al. unveil that the effector protein Cmi1 can be translocated into host cells and targets TBK1, thereby negatively regulating the host’s antifungal immune responses.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"6 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166298","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 : 2024-09-11DOI: 10.1016/j.chom.2024.08.011
Sheila Gonzalez, Maria G. Noval, Jessica M. Tucker
RNA G-quadruplexes are dynamically regulated during stress and infection. In this issue of Cell Host & Microbe, Schult et al.1 demonstrate that an RNA G-quadruplex conserved across orthoflaviviruses binds hnRNPH1 to mitigate the host stress response, highlighting the potential of this dynamic proviral RNA structure as a pan-flaviviral target.
{"title":"Stress less: Viral mastery of the RNA G-quadruplex","authors":"Sheila Gonzalez, Maria G. Noval, Jessica M. Tucker","doi":"10.1016/j.chom.2024.08.011","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.011","url":null,"abstract":"<p>RNA G-quadruplexes are dynamically regulated during stress and infection. In this issue of <em>Cell Host & Microbe</em>, Schult et al.<span><span><sup>1</sup></span></span> demonstrate that an RNA G-quadruplex conserved across orthoflaviviruses binds hnRNPH1 to mitigate the host stress response, highlighting the potential of this dynamic proviral RNA structure as a pan-flaviviral target.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"9 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166303","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 : 2024-09-10DOI: 10.1016/j.chom.2024.08.012
Sun-Young Kim, Justin R. Randall, Richard Gu, Quoc D. Nguyen, Bryan W. Davies
Microcins are small antibacterial proteins that mediate interbacterial competition. Their narrow-spectrum activity provides opportunities to discover microbiome-sparing treatments. However, microcins have been found almost exclusively in Enterobacteriaceae. Their broader existence and potential implications in other pathogens remain unclear. Here, we identify and characterize a microcin active against pathogenic Vibrio cholerae: MvcC. We show that MvcC is reliant on the outer membrane porin OmpT to cross the outer membrane. MvcC then binds the periplasmic protein OppA to reach and disrupt the cytoplasmic membrane. We demonstrate that MvcC’s cognate immunity protein is a protease, which precisely cleaves MvcC to neutralize its activity. Importantly, we show that MvcC is active against diverse cholera isolates and in a mouse model of V. cholerae colonization. Our results provide a detailed analysis of a microcin outside of Enterobacteriaceae and its potential to influence V. cholerae infection.
{"title":"Antibacterial action, proteolytic immunity, and in vivo activity of a Vibrio cholerae microcin","authors":"Sun-Young Kim, Justin R. Randall, Richard Gu, Quoc D. Nguyen, Bryan W. Davies","doi":"10.1016/j.chom.2024.08.012","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.012","url":null,"abstract":"<p>Microcins are small antibacterial proteins that mediate interbacterial competition. Their narrow-spectrum activity provides opportunities to discover microbiome-sparing treatments. However, microcins have been found almost exclusively in <em>Enterobacteriaceae</em>. Their broader existence and potential implications in other pathogens remain unclear. Here, we identify and characterize a microcin active against pathogenic <em>Vibrio cholerae</em>: MvcC. We show that MvcC is reliant on the outer membrane porin OmpT to cross the outer membrane. MvcC then binds the periplasmic protein OppA to reach and disrupt the cytoplasmic membrane. We demonstrate that MvcC’s cognate immunity protein is a protease, which precisely cleaves MvcC to neutralize its activity. Importantly, we show that MvcC is active against diverse cholera isolates and in a mouse model of <em>V. cholerae</em> colonization. Our results provide a detailed analysis of a microcin outside of <em>Enterobacteriaceae</em> and its potential to influence <em>V. cholerae</em> infection.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"48 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161032","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 : 2024-09-06DOI: 10.1016/j.chom.2024.08.007
Charlotte Wallaeys, Natalia Garcia-Gonzalez, Steven Timmermans, Jolien Vandewalle, Tineke Vanderhaeghen, Somara De Beul, Hester Dufoor, Melanie Eggermont, Elise Moens, Victor Bosteels, Riet De Rycke, Fabien Thery, Francis Impens, Serge Verbanck, Stefan Lienenklaus, Sophie Janssens, Richard S. Blumberg, Takao Iwawaki, Claude Libert
The cytokine tumor necrosis factor (TNF) plays important roles in limiting infection but is also linked to sepsis. The mechanisms underlying these paradoxical roles are unclear. Here, we show that TNF limits the antimicrobial activity of Paneth cells (PCs), causing bacterial translocation from the gut to various organs. This TNF-induced lethality does not occur in mice with a PC-specific deletion in the TNF receptor, P55. In PCs, TNF stimulates the IFN pathway and ablates the steady-state unfolded protein response (UPR), effects not observed in mice lacking P55 or IFNAR1. TNF triggers the transcriptional downregulation of IRE1 key genes Ern1 and Ern2, which are key mediators of the UPR. This UPR deficiency causes a significant reduction in antimicrobial peptide production and PC antimicrobial activity, causing bacterial translocation to organs and subsequent polymicrobial sepsis, organ failure, and death. This study highlights the roles of PCs in bacterial control and therapeutic targets for sepsis.
细胞因子肿瘤坏死因子(TNF)在限制感染方面发挥着重要作用,但也与败血症有关。这些矛盾作用的机制尚不清楚。在这里,我们发现 TNF 限制了 Paneth 细胞(PCs)的抗菌活性,导致细菌从肠道转移到各个器官。这种 TNF 诱导的致死现象不会发生在 TNF 受体 P55 PC 特异性缺失的小鼠身上。在 PC 中,TNF 可刺激 IFN 通路并消除稳态未折叠蛋白反应(UPR),而在缺乏 P55 或 IFNAR1 的小鼠中却观察不到这种效应。TNF 触发 IRE1 关键基因 Ern1 和 Ern2 的转录下调,而 Ern1 和 Ern2 是 UPR 的关键介质。这种 UPR 缺乏会导致抗菌肽的产生和 PC 的抗菌活性显著降低,从而引起细菌向器官转移,继而导致多微生物败血症、器官衰竭和死亡。这项研究强调了 PC 在细菌控制中的作用以及败血症的治疗靶点。
{"title":"Paneth cell TNF signaling induces gut bacterial translocation and sepsis","authors":"Charlotte Wallaeys, Natalia Garcia-Gonzalez, Steven Timmermans, Jolien Vandewalle, Tineke Vanderhaeghen, Somara De Beul, Hester Dufoor, Melanie Eggermont, Elise Moens, Victor Bosteels, Riet De Rycke, Fabien Thery, Francis Impens, Serge Verbanck, Stefan Lienenklaus, Sophie Janssens, Richard S. Blumberg, Takao Iwawaki, Claude Libert","doi":"10.1016/j.chom.2024.08.007","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.007","url":null,"abstract":"<p>The cytokine tumor necrosis factor (TNF) plays important roles in limiting infection but is also linked to sepsis. The mechanisms underlying these paradoxical roles are unclear. Here, we show that TNF limits the antimicrobial activity of Paneth cells (PCs), causing bacterial translocation from the gut to various organs. This TNF-induced lethality does not occur in mice with a PC-specific deletion in the TNF receptor, P55. In PCs, TNF stimulates the IFN pathway and ablates the steady-state unfolded protein response (UPR), effects not observed in mice lacking P55 or IFNAR1. TNF triggers the transcriptional downregulation of IRE1 key genes <em>Ern1</em> and <em>Ern2</em>, which are key mediators of the UPR. This UPR deficiency causes a significant reduction in antimicrobial peptide production and PC antimicrobial activity, causing bacterial translocation to organs and subsequent polymicrobial sepsis, organ failure, and death. This study highlights the roles of PCs in bacterial control and therapeutic targets for sepsis.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"48 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142864","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 : 2024-09-06DOI: 10.1016/j.chom.2024.08.010
Qisheng Gu, Marion Draheim, Cyril Planchais, Zihan He, Fan Mu, Shijie Gong, Chun Shen, Haitao Zhu, Dania Zhivaki, Khashayar Shahin, Jean-Marc Collard, Min Su, Xiaoming Zhang, Hugo Mouquet, Richard Lo-Man
The role of immunoglobulins produced by IL-10-producing regulatory B cells remains unknown. We found that a particular newborn regulatory B cell population (nBreg) negatively regulates the production of immunoglobulin M (IgM) via IL-10 in an autocrine manner, limiting the intensity of the polyreactive antibody response following innate activation. Based on nBreg scRNA-seq signature, we identify these cells and their repertoire in fetal and neonatal intestinal tissues. By characterizing 205 monoclonal antibodies cloned from intestinal nBreg, we show that newborn germline-encoded antibodies display reactivity against bacteria representing six different phyla of the early microbiota. nBreg-derived antibodies can influence the diversity and the cooperation between members of early microbial communities, at least in part by modulating energy metabolism. These results collectively suggest that nBreg populations help facilitate early-life microbiome establishment and shed light on the paradoxical activities of regulatory B cells in early life.
由产生 IL-10 的调节性 B 细胞产生的免疫球蛋白的作用仍然未知。我们发现,一种特殊的新生调节性 B 细胞群(nBreg)通过 IL-10 以自分泌的方式负向调节免疫球蛋白 M(IgM)的产生,从而限制先天激活后多反应性抗体反应的强度。根据 nBreg scRNA-seq 特征,我们确定了胎儿和新生儿肠道组织中的这些细胞和它们的复合物。通过对克隆自肠道 nBreg 的 205 种单克隆抗体进行鉴定,我们发现新生儿种系编码的抗体对代表早期微生物群六个不同门类的细菌具有反应性。nBreg 衍生的抗体可以影响早期微生物群落的多样性和成员之间的合作,至少部分是通过调节能量代谢来实现的。这些结果共同表明,nBreg 群体有助于促进生命早期微生物群的建立,并揭示了调节性 B 细胞在生命早期的矛盾活动。
{"title":"Intestinal newborn regulatory B cell antibodies modulate microbiota communities","authors":"Qisheng Gu, Marion Draheim, Cyril Planchais, Zihan He, Fan Mu, Shijie Gong, Chun Shen, Haitao Zhu, Dania Zhivaki, Khashayar Shahin, Jean-Marc Collard, Min Su, Xiaoming Zhang, Hugo Mouquet, Richard Lo-Man","doi":"10.1016/j.chom.2024.08.010","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.010","url":null,"abstract":"<p>The role of immunoglobulins produced by IL-10-producing regulatory B cells remains unknown. We found that a particular newborn regulatory B cell population (nBreg) negatively regulates the production of immunoglobulin M (IgM) via IL-10 in an autocrine manner, limiting the intensity of the polyreactive antibody response following innate activation. Based on nBreg scRNA-seq signature, we identify these cells and their repertoire in fetal and neonatal intestinal tissues. By characterizing 205 monoclonal antibodies cloned from intestinal nBreg, we show that newborn germline-encoded antibodies display reactivity against bacteria representing six different phyla of the early microbiota. nBreg-derived antibodies can influence the diversity and the cooperation between members of early microbial communities, at least in part by modulating energy metabolism. These results collectively suggest that nBreg populations help facilitate early-life microbiome establishment and shed light on the paradoxical activities of regulatory B cells in early life.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"2015 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142865","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 : 2024-09-06DOI: 10.1016/j.chom.2024.08.009
Si Liu, Shou-Wei Ding
Known for over a century, seed transmission of plant viruses promotes trans-continental virus dissemination and provides the source of infection to trigger devastating disease epidemics in crops. However, it remains unknown whether there is a genetically defined immune pathway to suppress virus vertical transmission in plants. Here, we demonstrate potent immunosuppression of cucumber mosaic virus (CMV) seed transmission in its natural host Arabidopsis thaliana by antiviral RNA interference (RNAi) pathway. Immunofluorescence microscopy reveals predominant embryo infection at four stages of embryo development. We show that antiviral RNAi confers resistance to seed infection with different genetic requirements and drastically enhanced potency compared with the inhibition of systemic infection of whole plants. Moreover, we detect efficient seed transmission of a mutant CMV lacking its RNAi suppressor gene in mutant plants defective in antiviral RNAi, providing further support for the immunosuppression of seed transmission by antiviral RNAi.
{"title":"Antiviral RNA interference inhibits virus vertical transmission in plants","authors":"Si Liu, Shou-Wei Ding","doi":"10.1016/j.chom.2024.08.009","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.009","url":null,"abstract":"<p>Known for over a century, seed transmission of plant viruses promotes trans-continental virus dissemination and provides the source of infection to trigger devastating disease epidemics in crops. However, it remains unknown whether there is a genetically defined immune pathway to suppress virus vertical transmission in plants. Here, we demonstrate potent immunosuppression of cucumber mosaic virus (CMV) seed transmission in its natural host <em>Arabidopsis thaliana</em> by antiviral RNA interference (RNAi) pathway. Immunofluorescence microscopy reveals predominant embryo infection at four stages of embryo development. We show that antiviral RNAi confers resistance to seed infection with different genetic requirements and drastically enhanced potency compared with the inhibition of systemic infection of whole plants. Moreover, we detect efficient seed transmission of a mutant CMV lacking its RNAi suppressor gene in mutant plants defective in antiviral RNAi, providing further support for the immunosuppression of seed transmission by antiviral RNAi.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"18 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142866","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 : 2024-08-29DOI: 10.1016/j.chom.2024.08.004
Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C. Stinson, Mohamed A. Jamal, Miriam R. Ortega, Christopher A. Sanchez, Saira S. Ahmed, Jennifer L. Karmouch, Chia-Chi Chang, Ivonne I. Flores, Lauren K. McDaniel, Alexandria N. Brown, Rawan K. El-Himri, Valerie A. Chapa, Lin Tan, Bao Q. Tran, Yao Xiao, Christopher Fan, Dung Pham, Robert R. Jenq
Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.
{"title":"Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease","authors":"Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C. Stinson, Mohamed A. Jamal, Miriam R. Ortega, Christopher A. Sanchez, Saira S. Ahmed, Jennifer L. Karmouch, Chia-Chi Chang, Ivonne I. Flores, Lauren K. McDaniel, Alexandria N. Brown, Rawan K. El-Himri, Valerie A. Chapa, Lin Tan, Bao Q. Tran, Yao Xiao, Christopher Fan, Dung Pham, Robert R. Jenq","doi":"10.1016/j.chom.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.004","url":null,"abstract":"<p>Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (<em>n</em> = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of <em>Bacteroides ovatus</em>. In a murine GVHD model aggravated by carbapenem antibiotics, introducing <em>B. ovatus</em> reduced GVHD severity and improved survival. These beneficial effects of <em>Bacteroides ovatus</em> were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as <em>Bacteroides thetaiotaomicron</em> and <em>Akkermansia muciniphila</em>, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of <em>B. ovatus</em>.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"8 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090512","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 : 2024-08-29DOI: 10.1016/j.chom.2024.08.003
Amy M. Peiper, Joyce Morales Aparicio, Zhengzheng Hu, Lufuno Phophi, Emily W. Helm, Rebecca J. Rubinstein, Matthew Phillips, Caroline G. Williams, Saravanan Subramanian, Michael Cross, Neha Iyer, Quyen Nguyen, Rachel Newsome, Christian Jobin, Stephanie N. Langel, Filemon Bucardo, Sylvia Becker-Dreps, Xiao-Di Tan, Paul A. Dawson, Stephanie M. Karst
The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Working in an infant mouse model of norovirus infection, we demonstrate that microbiota and their bile acid metabolites protect from norovirus diarrhea, whereas host bile acids promote disease. We also find that maternal bile acid metabolism determines the susceptibility of newborn mice to norovirus diarrhea during breastfeeding. Finally, targeting maternal and neonatal bile acid metabolism can protect newborn mice from norovirus disease. In summary, neonatal metabolic immaturity and breastmilk bile acids are central determinants of heightened newborn vulnerability to norovirus disease.
{"title":"Metabolic immaturity and breastmilk bile acid metabolites are central determinants of heightened newborn vulnerability to norovirus diarrhea","authors":"Amy M. Peiper, Joyce Morales Aparicio, Zhengzheng Hu, Lufuno Phophi, Emily W. Helm, Rebecca J. Rubinstein, Matthew Phillips, Caroline G. Williams, Saravanan Subramanian, Michael Cross, Neha Iyer, Quyen Nguyen, Rachel Newsome, Christian Jobin, Stephanie N. Langel, Filemon Bucardo, Sylvia Becker-Dreps, Xiao-Di Tan, Paul A. Dawson, Stephanie M. Karst","doi":"10.1016/j.chom.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.003","url":null,"abstract":"<p>The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Working in an infant mouse model of norovirus infection, we demonstrate that microbiota and their bile acid metabolites protect from norovirus diarrhea, whereas host bile acids promote disease. We also find that maternal bile acid metabolism determines the susceptibility of newborn mice to norovirus diarrhea during breastfeeding. Finally, targeting maternal and neonatal bile acid metabolism can protect newborn mice from norovirus disease. In summary, neonatal metabolic immaturity and breastmilk bile acids are central determinants of heightened newborn vulnerability to norovirus disease.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"57 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090514","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 : 2024-08-28DOI: 10.1016/j.chom.2024.08.002
Jean Cury, Matthieu Haudiquet, Veronica Hernandez Trejo, Ernest Mordret, Anael Hanouna, Maxime Rotival, Florian Tesson, Delphine Bonhomme, Gal Ofir, Lluis Quintana-Murci, Philippe Benaroch, Enzo Z. Poirier, Aude Bernheim
Deciphering the immune organization of eukaryotes is important for human health and for understanding ecosystems. The recent discovery of antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. However, whether bacterial antiphage proteins can illuminate immune organization in eukaryotes remains unexplored. Here, we use a phylogeny-driven approach to uncover eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes and maintain a role in human immunity. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionarily linked to the antiphage system Mokosh. Additionally, human GTPases of immunity-associated proteins (GIMAPs) as well as two genes encoded in microsynteny, FHAD1 and CTRC, are respectively related to the Eleos and Lamassu prokaryotic systems and exhibit antiviral activity. Our work illustrates how comparative genomics of immune mechanisms can uncover defense genes in eukaryotes.
{"title":"Conservation of antiviral systems across domains of life reveals immune genes in humans","authors":"Jean Cury, Matthieu Haudiquet, Veronica Hernandez Trejo, Ernest Mordret, Anael Hanouna, Maxime Rotival, Florian Tesson, Delphine Bonhomme, Gal Ofir, Lluis Quintana-Murci, Philippe Benaroch, Enzo Z. Poirier, Aude Bernheim","doi":"10.1016/j.chom.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.002","url":null,"abstract":"<p>Deciphering the immune organization of eukaryotes is important for human health and for understanding ecosystems. The recent discovery of antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. However, whether bacterial antiphage proteins can illuminate immune organization in eukaryotes remains unexplored. Here, we use a phylogeny-driven approach to uncover eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes and maintain a role in human immunity. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionarily linked to the antiphage system Mokosh. Additionally, human GTPases of immunity-associated proteins (GIMAPs) as well as two genes encoded in microsynteny, FHAD1 and CTRC, are respectively related to the Eleos and Lamassu prokaryotic systems and exhibit antiviral activity. Our work illustrates how comparative genomics of immune mechanisms can uncover defense genes in eukaryotes.</p>","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"5 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085507","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}