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Got bile? Breastmilk bile acids influence norovirus infection 有胆汁吗?母乳胆汁酸影响诺如病毒感染
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-11 DOI: 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

母乳喂养对多种病原体的感染有保护作用,但对诺罗病毒却没有保护作用。造成这种差异的机制尚不清楚。在本期《细胞、宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Peiper 等人证明,虽然母乳能保护小鼠免受肠道损伤,但由于母源胆汁酸的作用,母乳能促进新生小鼠感染诺如病毒。
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引用次数: 0
Stealth strategies of Candida albicans to evade host immunity 白色念珠菌逃避宿主免疫的隐形策略
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-11 DOI: 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.

在机会性致病过程中,白色念珠菌会采用经典策略,如酵母到芽孢的转化和免疫原性掩蔽。在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Luo 等人揭示了效应蛋白 Cmi1 可转运到宿主细胞内并靶向 TBK1,从而负向调节宿主的抗真菌免疫反应。
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引用次数: 0
Stress less: Viral mastery of the RNA G-quadruplex 减轻压力:病毒驾驭 RNA G 型四联体
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-11 DOI: 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.

RNA G-四链体在应激和感染过程中受到动态调节。在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Schult 等人1 证明了一种在正黄病毒中保留下来的 RNA G-四链体能与 hnRNPH1 结合,从而减轻宿主的应激反应,凸显了这种动态前病毒 RNA 结构作为泛黄病毒靶标的潜力。
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引用次数: 0
Antibacterial action, proteolytic immunity, and in vivo activity of a Vibrio cholerae microcin 霍乱弧菌微霉素的抗菌作用、蛋白水解免疫和体内活性
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-10 DOI: 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.

微球蛋白是一种小型抗菌蛋白,可介导细菌间的竞争。它们的窄谱活性为发现保护微生物的治疗方法提供了机会。然而,微球蛋白几乎只在肠杆菌科细菌中发现。它们在其他病原体中的广泛存在和潜在影响仍不清楚。在这里,我们鉴定并描述了一种对致病性霍乱弧菌具有活性的微霉素:MvcC。我们发现 MvcC 依靠外膜孔蛋白 OmpT 穿过外膜。然后,MvcC 与围质膜蛋白 OppA 结合,到达并破坏细胞质膜。我们证明 MvcC 的同源免疫蛋白是一种蛋白酶,它能精确地裂解 MvcC 以中和其活性。重要的是,我们发现 MvcC 对多种霍乱分离菌株和霍乱弧菌小鼠定植模型都有活性。我们的研究结果详细分析了肠杆菌科以外的一种微量蛋白酶及其影响霍乱弧菌感染的潜力。
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引用次数: 0
Paneth cell TNF signaling induces gut bacterial translocation and sepsis Paneth 细胞 TNF 信号诱导肠道细菌迁移和败血症
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-06 DOI: 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。
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引用次数: 0
Intestinal newborn regulatory B cell antibodies modulate microbiota communities 肠道新生调节性 B 细胞抗体调节微生物群落
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-06 DOI: 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。
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引用次数: 0
Antiviral RNA interference inhibits virus vertical transmission in plants 抗病毒 RNA 干扰可抑制病毒在植物体内的垂直传播
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-06 DOI: 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.

一个多世纪以来,植物病毒的种子传播促进了病毒的跨洲传播,并提供了引发作物毁灭性病害流行的感染源。然而,是否存在一种基因定义的免疫途径来抑制病毒在植物中的垂直传播仍是未知数。在这里,我们通过抗病毒 RNA 干扰(RNAi)途径证明了黄瓜花叶病毒(CMV)在其天然宿主拟南芥中种子传播的强效免疫抑制。免疫荧光显微镜显示,在胚胎发育的四个阶段,胚胎感染占主导地位。我们发现,抗病毒 RNAi 对种子感染的抗性有不同的遗传要求,与抑制整株植物的系统感染相比,其效力大大增强。此外,我们还在抗病毒 RNAi 缺陷的突变植株中检测到了缺乏 RNAi 抑制基因的突变 CMV 的高效种子传播,从而进一步证实了抗病毒 RNAi 对种子传播的免疫抑制作用。
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引用次数: 0
Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease 卵形乳杆菌能缓解微生物群落失调引起的移植物抗宿主疾病
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-29 DOI: 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.

急性下胃肠道GVHD(aLGI-GVHD)是异基因造血干细胞移植的一种严重并发症。虽然肠道微生物群与aLGI-GVHD的发病率有关,但肠道微生物群如何影响aLGI-GVHD的治疗反应尚未得到深入研究。在一组 aLGI-GVHD 患者(n = 37)中,我们发现,对皮质类固醇标准疗法无反应与之前使用碳青霉烯类抗生素治疗和粪便微生物群紊乱有关,粪便微生物群紊乱的特点是卵形乳杆菌丰度降低。在一种因碳青霉烯类抗生素而恶化的小鼠 GVHD 模型中,引入卵形乳杆菌可降低 GVHD 的严重程度并提高存活率。卵形乳杆菌的这些有益作用与它能将食物中的多糖代谢成单糖有关,单糖能抑制结肠粘液降解菌(如Bacteroides thetaiotaomicron和Akkermansia muciniphila)的粘液降解能力,从而降低与GVHD相关的死亡率。总之,这些发现揭示了微生物群在 aLGI-GVHD 中的重要性以及 B. ovatus 的治疗潜力。
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引用次数: 0
Metabolic immaturity and breastmilk bile acid metabolites are central determinants of heightened newborn vulnerability to norovirus diarrhea 代谢不成熟和母乳胆汁酸代谢物是新生儿更易感染诺如病毒腹泻的核心决定因素
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-29 DOI: 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.

肠道病毒感染的致病结果由病毒、肠道微生物群和宿主免疫因素之间复杂的相互作用所决定,而代谢物则是其中的关键介质。诺罗病毒与胆汁酸代谢物结合,胆汁酸由宿主产生,然后被共生细菌修饰。令人费解的是,胆汁酸在诺如病毒感染过程中既能起到挑衅病毒的作用,也能起到抗病毒的作用。在诺如病毒感染的婴儿小鼠模型中,我们证明微生物群及其胆汁酸代谢物可以防止诺如病毒腹泻,而宿主胆汁酸则会促进疾病的发生。我们还发现,母体胆汁酸代谢决定了新生小鼠在母乳喂养期间对诺如病毒腹泻的易感性。最后,针对母体和新生儿的胆汁酸代谢可以保护新生小鼠免受诺如病毒疾病的侵袭。总之,新生儿代谢不成熟和母乳胆汁酸是新生儿更易感染诺如病毒疾病的核心决定因素。
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引用次数: 0
Conservation of antiviral systems across domains of life reveals immune genes in humans 跨生命领域的抗病毒系统保护揭示了人类的免疫基因
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-08-28 DOI: 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.

破译真核生物的免疫组织对于人类健康和了解生态系统非常重要。最近发现的抗虹吸系统揭示了各种真核生物免疫蛋白源自原核生物抗虹吸系统。然而,细菌的抗虹吸蛋白是否能揭示真核生物的免疫组织仍有待探索。在这里,我们利用系统发育驱动的方法,通过寻找细菌抗虹吸系统的同源物来发现真核生物的免疫蛋白。我们证明,与最近发现的抗虹吸系统具有序列相似性的蛋白质广泛存在于真核生物中,并在人类免疫中发挥作用。抗转座子 piRNA 途径中的两个真核生物蛋白在进化上与抗虹吸系统 Mokosh 有关。此外,人类免疫相关蛋白 GTPases(GIMAPs)以及微合成中编码的两个基因 FHAD1 和 CTRC 分别与 Eleos 和 Lamassu 原核系统有关,并表现出抗病毒活性。我们的工作说明了免疫机制比较基因组学如何发现真核生物的防御基因。
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引用次数: 0
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