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Vaginal lactobacilli produce anti-inflammatory β-carboline compounds 阴道乳酸菌产生抗炎的β-咔啉化合物
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-17 DOI: 10.1016/j.chom.2024.09.014
Virginia J. Glick, Cecilia A. Webber, Lauren E. Simmons, Morgan C. Martin, Maryam Ahmad, Cecilia H. Kim, Amanda N.D. Adams, Sunghee Bang, Michael C. Chao, Nicole C. Howard, Sarah M. Fortune, Manasvi Verma, Marco Jost, Lalit K. Beura, Michael J. James, Seo Yoon Lee, Caroline M. Mitchell, Jon Clardy, Ki Hyun Kim, Smita Gopinath
The optimal vaginal microbiome is a Lactobacillus-dominant community. Apart from Lactobacillus iners, the presence of Lactobacillus species is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of Lactobacillus-dominance is associated with inflammatory conditions, such as bacterial vaginosis (BV). We have identified that Lactobacillus crispatus, a key vaginal bacterial species, produces a family of β-carboline compounds with anti-inflammatory activity. These compounds suppress nuclear factor κB (NF-κB) and interferon (IFN) signaling downstream of multiple pattern recognition receptors in primary human cells and significantly dampen type I IFN receptor (IFNAR) activation in monocytes. Topical application of an anti-inflammatory β-carboline compound, perlolyrine, was sufficient to significantly reduce vaginal inflammation in a mouse model of genital herpes infection. These compounds are enriched in cervicovaginal lavage (CVL) of healthy people compared with people with BV. This study identifies a family of compounds by which vaginal lactobacilli mediate host immune homeostasis and highlights a potential therapeutic avenue for vaginal inflammation.
最佳的阴道微生物群落是以乳酸杆菌为主的群落。除乳酸杆菌茵外,乳酸杆菌的存在还与阴道炎症的减少和促炎症细胞因子水平的降低有关。乳酸杆菌优势的丧失与炎症有关,如细菌性阴道病(BV)。我们发现,脆片乳杆菌是一种重要的阴道细菌,它能产生一系列具有抗炎活性的β-咔啉化合物。这些化合物能抑制原代人体细胞中多种模式识别受体下游的核因子κB(NF-κB)和干扰素(IFN)信号传导,并能显著抑制单核细胞中 IFN 受体(IFNAR)的活化。在生殖器疱疹感染的小鼠模型中,局部应用抗炎的β-咔啉化合物perlolyrine足以显著减轻阴道炎症。与 BV 患者相比,健康人的宫颈阴道灌洗液(CVL)中富含这些化合物。这项研究确定了阴道乳酸杆菌介导宿主免疫平衡的化合物家族,并强调了治疗阴道炎症的潜在途径。
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引用次数: 0
Gut symbiont-derived anandamide promotes reward learning in honeybees by activating the endocannabinoid pathway 源自肠道共生菌的安乃近通过激活内源性大麻素途径促进蜜蜂的奖赏学习
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-16 DOI: 10.1016/j.chom.2024.09.013
Zhaopeng Zhong, Xiaohuan Mu, Haoyu Lang, Yueyi Wang, Yanling Jiang, Yuwen Liu, Qian Zeng, Siyuan Xia, Baotong Zhang, Zilong Wang, Xiaofei Wang, Hao Zheng
Polyunsaturated fatty acids (PUFAs) are dietary components participating in neurotransmission and cell signaling. Pollen is a source of PUFAs for honeybees, and disruptions in dietary PUFAs reduce the cognitive performance of honeybees. We reveal that gut bacteria of honeybees contribute to fatty acid metabolism, impacting reward learning. Gut bacteria possess Δ-6 desaturases that mediate fatty acid elongation and compensate for the absence of honeybee factors required for fatty acid metabolism. Colonization with Gilliamella apicola, but not a mutant lacking the Δ-6 desaturase FADS2, increases the production of anandamide (AEA), a ligand of the endocannabinoid system, and alters learning and memory. AEA activates the Hymenoptera-specific transient receptor AmHsTRPA in astrocytes, which induces Ca2+ influx and regulates glutamate re-uptake of glial cells to enhance reward learning. These findings illuminate the roles of gut symbionts in host fatty acid metabolism and the impacts of endocannabinoid signaling on the reward system of social insects.
多不饱和脂肪酸(PUFA)是参与神经传递和细胞信号传导的膳食成分。花粉是蜜蜂的多不饱和脂肪酸来源之一,而膳食中的多不饱和脂肪酸会降低蜜蜂的认知能力。我们发现,蜜蜂的肠道细菌有助于脂肪酸代谢,从而影响奖励学习。肠道细菌拥有介导脂肪酸伸长的Δ-6去饱和酶,可弥补蜜蜂脂肪酸代谢所需因子的缺失。蜜蜂定殖 Gilliamella apicola(但不是缺乏 Δ-6 去饱和酶 FADS2 的突变体)会增加内源性大麻素系统的配体--anandamide(AEA)的产生,并改变学习和记忆。AEA能激活星形胶质细胞中的蝶呤特异性瞬时受体AmHsTRPA,从而诱导Ca2+流入并调节胶质细胞对谷氨酸的再摄取,从而提高奖赏学习能力。这些发现阐明了肠道共生体在宿主脂肪酸代谢中的作用以及内源性大麻素信号对社会性昆虫奖赏系统的影响。
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引用次数: 0
SINE RNA of the imprinted miRNA clusters mediates constitutive type III interferon expression and antiviral protection in hemochorial placentas 印迹 miRNA 簇的 SINE RNA 在血胎中介导组成型 III 型干扰素的表达和抗病毒保护
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-12 DOI: 10.1016/j.chom.2024.10.003
Ishani Wickramage, Jeffrey VanWye, Klaas Max, John H. Lockhart, Ismet Hortu, Ezinne F. Mong, John Canfield, Hiran M. Lamabadu Warnakulasuriya Patabendige, Ozlem Guzeloglu-Kayisli, Kimiko Inoue, Atsuo Ogura, Charles J. Lockwood, Kemal M. Akat, Thomas Tuschl, Umit A. Kayisli, Hana Totary-Jain
(Cell Host & Microbe 31, 1185–1199.e1–e10; July 12, 2023)
(Cell Host & Microbe 31, 1185-1199.e1-e10; July 12, 2023)。
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引用次数: 0
Hospitalization throws the preterm gut microbiome off-key 住院治疗使早产儿肠道微生物群失调
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.009
Jing Qian, Emily N. Yeo, Matthew R. Olm
Environmental exposures substantially influence the infant gut microbiome. In this issue of Cell Host & Microbe, Thänert et al.1 characterize how medical interventions in the neonatal intensive care unit (NICU) shape gut microbiome dynamics in the first months of life by analyzing over 2,500 fecal samples with metagenomics and metatranscriptomics.
环境暴露会对婴儿肠道微生物组产生重大影响。在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Thänert 等人1 通过元基因组学和元转录组学分析了 2500 多份粪便样本,描述了新生儿重症监护室(NICU)的医疗干预措施如何影响婴儿出生后最初几个月的肠道微生物组动态。
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引用次数: 0
Gut microbiome and bladder cancer: A new link through nitrosamine metabolism 肠道微生物群与膀胱癌:亚硝胺代谢的新联系
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.003
Sridhar Mani
A recent Nature paper1 reveals that gut microbes metabolize N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) into the bladder carcinogen N-n-butyl-N-(3-carboxypropyl)-nitrosamine (BCPN) in the intestines, establishing a direct link between gut microbial activity and the development of bladder cancer.
最近的一篇《自然》(Nature)论文1 揭示,肠道微生物会在肠道中将 N-丁基-N-(4-羟基丁基)-亚硝胺(BBN)代谢为膀胱致癌物 N-丁基-N-(3-羧基丙基)-亚硝胺(BCPN),从而建立了肠道微生物活动与膀胱癌发病之间的直接联系。
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引用次数: 0
MX2 forms nucleoporin-comprising cytoplasmic biomolecular condensates that lure viral capsids MX2 形成由核蛋白组成的细胞质生物分子凝聚体,引诱病毒外壳
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.002
George D. Moschonas, Louis Delhaye, Robin Cooreman, Franziska Hüsers, Anayat Bhat, Zoe Stylianidou, Elien De Bousser, Laure De Pryck, Hanna Grzesik, Delphine De Sutter, Eef Parthoens, Anne-Sophie De Smet, Aleksandra Maciejczuk, Saskia Lippens, Nico Callewaert, Linos Vandekerckhove, Zeger Debyser, Beate Sodeik, Sven Eyckerman, Xavier Saelens
Human myxovirus resistance 2 (MX2) can restrict HIV-1 and herpesviruses at a post-entry step through a process requiring an interaction between MX2 and the viral capsids. The involvement of other host cell factors, however, remains poorly understood. Here, we mapped the proximity interactome of MX2, revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacted with these proteins to form multiprotein cytoplasmic biomolecular condensates that were essential for its anti-HIV-1 and anti-herpes simplex virus 1 (HSV-1) activity. MX2 condensate formation required the disordered N-terminal region and MX2 dimerization. Incoming HIV-1 and HSV-1 capsids associated with MX2 at these dynamic cytoplasmic biomolecular condensates, preventing nuclear entry of their viral genomes. Thus, MX2 forms cytoplasmic condensates that likely act as nuclear pore decoys, trapping capsids and inducing premature viral genome release to interfere with nuclear targeting of HIV-1 and HSV-1.
人类肌瘤病毒抵抗力 2(MX2)可通过 MX2 与病毒外壳之间的相互作用,在进入后阶段限制 HIV-1 和疱疹病毒。然而,人们对其他宿主细胞因子的参与仍然知之甚少。在这里,我们绘制了 MX2 的近距离相互作用组,发现与核孔复合体有关的富含苯丙氨酸-甘氨酸(FG)的蛋白质以及作为细胞质核糖核蛋白颗粒一部分的蛋白质大量富集。MX2 与这些蛋白相互作用,形成多蛋白细胞质生物分子凝聚体,这对其抗 HIV-1 和抗单纯疱疹病毒 1(HSV-1)的活性至关重要。MX2 凝聚物的形成需要无序的 N 端区域和 MX2 的二聚化。传入的 HIV-1 和 HSV-1 包囊与 MX2 在这些动态的细胞质生物分子凝聚体上结合,阻止了病毒基因组进入细胞核。因此,MX2 形成的细胞质凝聚体可能充当核孔诱饵,诱捕噬菌体并诱导病毒基因组过早释放,从而干扰 HIV-1 和 HSV-1 的核靶向作用。
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引用次数: 0
RNAi, a sword of plant seeds to combat viral infections RNAi,植物种子对抗病毒感染的利剑
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.08.019
Yan Wang, Yule Liu
Vertical transmission of plant viruses through seeds has been known for a century, yet the mechanism for seeds to combat viral infection remains unclear. In this issue of Cell Host & Microbe, Liu and Ding demonstrate the genetic requirement of RNA silencing (RNAi) pathway for plants to suppress seed transmission.
植物病毒通过种子垂直传播已有百年历史,但种子抗病毒感染的机制仍不清楚。在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,刘和丁(音译)证明了植物抑制种子传播所需的 RNA 沉默(RNAi)遗传途径。
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引用次数: 0
Bacteria renew an OLD protein to cleave host tRNAs and block phage translation 细菌更新一种古老的蛋白质,以裂解宿主 tRNA 并阻止噬菌体翻译
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.006
Kyle D. Gibbs, Michele LeRoux
Anti-phage defenses must rapidly sense and respond to diverse viruses. A recent pair of papers in Nature reveal via structural and functional assays how the PARIS defense system, a recently discovered toxin-antitoxin system, senses phage-associated molecular patterns (PhAMPs), thereby activating an endonuclease toxin that cleaves tRNA to block phage replication.
抗噬菌体防御系统必须迅速感知并应对各种病毒。最近发表在《自然》(Nature)上的两篇论文通过结构和功能测试揭示了 PARIS 防御系统(一种最近发现的毒素-抗毒素系统)如何感知噬菌体相关分子模式(PhAMPs),从而激活内切酶毒素,裂解 tRNA 以阻止噬菌体复制。
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引用次数: 0
Mimicry games: NPC-like MX2 condensates trap viruses 模仿游戏类似 NPC 的 MX2 凝聚物捕获病毒
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.001
Junfeng Zhou, Wei Wei
Recent findings suggest that HIV-1 capsids mimic nuclear transport receptors to engage FG-nucleoporins for entry into host nuclei. In this issue of Cell Host & Microbe, Moschonas et al. report that MX2 forms cytoplasmic condensates comprising FG-nucleoporins resembling nuclear pore complexes to capture viral capsids and hinder their nuclear transport.
最近的研究结果表明,HIV-1 的噬菌体能模拟核转运受体,使 FG 核蛋白参与进入宿主细胞核。在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Moschonas 等人报告说,MX2 形成了由类似核孔复合体的 FG-核orins 组成的细胞质凝聚体,以捕获病毒衣壳并阻碍其核运输。
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引用次数: 0
To sense or not to sense, Paneth cell regulation of mucosal immunity 感知或不感知,Paneth 细胞对粘膜免疫的调控
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1016/j.chom.2024.09.005
Sebastian Weis, Irah L. King, Wolfgang Vivas
Paneth cells located within intestinal crypts support epithelial stem cells and immunity through growth factors and antimicrobial peptides. In this issue of Cell Host & Microbe, Wallaeys et al. report that TNF sensing by Paneth cells disrupts the unfolded protein response and decreases antimicrobial peptides, causing bacterial translocation and sepsis.
位于肠隐窝内的Paneth细胞通过生长因子和抗菌肽支持上皮干细胞和免疫。在本期《细胞、宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Wallaeys 等人报告说,Paneth 细胞对 TNF 的感应会破坏未折叠蛋白反应并减少抗菌肽,从而导致细菌转移和败血症。
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引用次数: 0
期刊
Cell host & microbe
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