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TGEV nonstructural protein ORF3b upregulates the expression of SLA-DR at the transcriptional level in monocyte-derived porcine dendritic cells. TGEV非结构蛋白ORF3b可在转录水平上上调单核细胞衍生猪树突状细胞中SLA-DR的表达。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-13 DOI: 10.1016/j.micinf.2024.105437
Hang Liu, Mengyao Ma, Xinhao Jia, Mengwei Qian, Bo Pang, Muzi Li, Honglei Zhang, Shijie Ma, Lanlan Zheng

Transmissible gastroenteritis virus (TGEV) is a porcine intestinal pathogenic coronavirus that can cause acute intestinal diseases in pigs, especially in suckling piglets under two weeks of age, with a mortality rate of 100 %. Dendritic cells (DCs) are important antigen-presenting cells (APCs) that are essential for the initiation and modulation of immune responses in animals. In this study, we used monocyte-derived porcine DCs as an in vitro model of APCs to further study the pathogenic mechanism of TGEV. Our results demonstrated that TGEV successfully replicates in monocyte-derived porcine DCs, whereas UV-inactivated TGEV failed to infect these cells. Importantly, TGEV infection of DCs led to significant upregulation of swine leukocyte antigen II DR (SLA-DR), a key molecule in the major histocompatibility complex class II (MHC-II) family. We further demonstrated that the ORF3b nonstructural protein of TGEV significantly enhances SLA-DR expression at the transcriptional level in porcine DCs. This study provides new insights into the pathogenic mechanisms of TGEV.

传染性胃肠炎病毒(TGEV)是一种猪肠道致病性冠状病毒,可引起猪的急性肠道疾病,尤其是两周龄以下的哺乳仔猪,死亡率高达 100%。树突状细胞(DC)是重要的抗原递呈细胞(APC),对动物免疫反应的启动和调节至关重要。在本研究中,我们使用单核细胞衍生的猪 DCs 作为体外 APCs 模型,进一步研究 TGEV 的致病机制。我们的研究结果表明,TGEV 能在单核细胞衍生的猪 DCs 中成功复制,而紫外线灭活的 TGEV 却不能感染这些细胞。重要的是,TGEV 感染 DCs 会导致猪白细胞抗原 II DR(SLA-DR)显著上调,而猪白细胞抗原 II DR 是主要组织相容性复合体 II 类(MHC-II)家族中的一个关键分子。我们进一步证实,TGEV 的 ORF3b 非结构蛋白在转录水平上显著增强了猪 DCs 中 SLA-DR 的表达。这项研究为了解 TGEV 的致病机制提供了新的视角。
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引用次数: 0
miRNAs regulate the metabolic adaptation of Paracoccidioides brasiliensis during copper deprivation. miRNA调控巴西副球孢子虫在铜匮乏期间的代谢适应。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-09 DOI: 10.1016/j.micinf.2024.105435
Dener Lucas Araújo Dos Santos, Juliana Santana de Curcio, Evandro Novaes, Célia Maria de Almeida Soares

Copper is an essential metal for cellular processes such as detoxification of reactive oxygen species, oxidative phosphorylation, and iron uptake. However, during infection, the host restricts the bioavailability of this micronutrient to the pathogen as a strategy to combat infection. Recently, we have shown the involvement of miRNAs as an adaptive strategy of P. brasiliensis upon metal deprivation such as iron and zinc. However, their role in copper limitation still needs to be elucidated. Our objective was to characterize the expression profile of miRNAs regulated during copper deprivation in P. brasiliensis and the putative altered processes. Through RNAseq analysis and bioinformatics, we identified 14 differentially expressed miRNAs, two of which putatively regulated oxidative stress response, beta-oxidation, glyoxylate cycle, and cell wall remodeling. Our results suggest that metabolic adaptations carried out by P. brasiliensis in copper deprivation are regulated by miRNAs.

铜是活性氧解毒、氧化磷酸化和铁吸收等细胞过程所必需的金属。然而,在感染期间,宿主会限制病原体对这种微量元素的生物利用率,以此作为一种抗感染策略。最近,我们发现在铁和锌等金属匮乏的情况下,miRNAs 参与了 P. brasiliensis 的适应性策略。然而,它们在铜限制中的作用仍有待阐明。我们的目的是描述铜缺乏时巴西蘑菇中受调控的 miRNAs 的表达谱及其可能的改变过程。通过 RNAseq 分析和生物信息学研究,我们发现了 14 个表达不同的 miRNA,其中两个可能调控氧化应激反应、β-氧化、乙醛酸循环和细胞壁重塑。我们的研究结果表明,巴西鹅膏菌在铜缺乏条件下的代谢适应受 miRNAs 的调控。
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引用次数: 0
Bad company? The pericardium microbiome in people investigated for tuberculous pericarditis in an HIV-prevalent setting. 坏伙伴?在艾滋病流行的环境中,接受结核性心包炎调查者的心包微生物组。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-09 DOI: 10.1016/j.micinf.2024.105434
Georgina Nyawo, Charissa C Naidoo, Benjamin G Wu, Benjamin Kwok, Jose C Clemente, Yonghua Li, Stephanie Minnies, Byron Reeve, Suventha Moodley, Thadathilankal-Jess John, Sumanth Karamchand, Shivani Singh, Alfonso Pecararo, Anton Doubell, Charles Kyriakakis, Robin Warren, Leopoldo N Segal, Grant Theron

Background: The site-of-disease microbiome and predicted metagenome were evaluated in a cross-sectional study involving people with presumptive tuberculous pericarditis. We also explored the interaction between C-reactive protein (CRP) and the microbiome.

Methods: People with effusions requiring diagnostic pericardiocentesis (n=139) provided pericardial fluid for sequencing and blood for CRP measurement.

Results: Pericardial fluid microbiota differed in β-diversity among people with definite (dTB, n=91), probable (pTB, n=25), and non- (nTB, n=23) tuberculous pericarditis. dTBs were Mycobacterium-, Lacticigenium-, and Kocuria-enriched vs. nTBs. HIV-positive dTBs were Mycobacterium-, Bifidobacterium-, Methylobacterium-, and Leptothrix-enriched vs. HIV-negative dTBs. HIV-positive dTBs on ART were Mycobacterium- and Bifidobacterium-depleted vs. those not on ART. dTBs exhibited enrichment in short-chain fatty acid (SCFA) and mycobacterial metabolism pathways vs. nTBs. Additional non-pericardial involvement (pulmonary infiltrates) was associated with Mycobacterium-enrichment and Streptococcus-depletion. Mycobacterium reads were in 34 % (31/91) of dTBs, 8 % (2/25) of pTBs and 17 % (4/23) nTBs. People with CRP above (vs. below) the median value had different β-diversity (Pseudomonas-depleted). No correlation was found between enriched taxa in dTBs and CRP.

Conclusions: Pericardial fluid microbial composition varies by tuberculosis status, HIV (and ART) status and dTBs are enriched in SCFA-associated taxa. The clinical significance, including mycobacterial reads in nTBs and pTBs, requires evaluation.

背景:在一项横断面研究中,我们对推测患有结核性心包炎的患者进行了疾病部位微生物组和预测元基因组的评估。我们还探讨了C反应蛋白(CRP)与微生物组之间的相互作用:方法:需要进行诊断性心包穿刺术的积液患者(139 人)提供心包液进行测序,并提供血液进行 CRP 测量:在确诊(dTB,n=91)、可能(pTB,n=25)和非(nTB,n=23)结核性心包炎患者中,心包积液微生物群在β多样性方面存在差异。艾滋病毒阳性的 dTB 与艾滋病毒阴性的 dTB 相比,富含分枝杆菌、双歧杆菌、甲基分支杆菌和钩端螺旋体。与未接受抗逆转录病毒疗法的 dTBs 相比,接受抗逆转录病毒疗法的 HIV 阳性 dTBs 分枝杆菌和双歧杆菌减少。额外的非心包受累(肺部浸润)与分枝杆菌富集和链球菌减少有关。34%(31/91)的dTBs、8%(2/25)的pTBs和17%(4/23)的nTBs存在分枝杆菌读数。CRP 高于(或低于)中位值的人群具有不同的 β 多样性(假单胞菌贫化)。dTBs 中富集的分类群与 CRP 之间没有相关性:结论:心包积液微生物组成因结核病状态、HIV(和抗逆转录病毒疗法)状态而异,dTBs 中富含 SCFA 相关类群。其临床意义(包括nTBs和pTBs中的分枝杆菌读数)需要进行评估。
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引用次数: 0
Unraveling the role of human microglia in tick-borne encephalitis virus infection: insights into neuroinflammation and viral pathogenesis 揭示人类小胶质细胞在蜱传脑炎病毒感染中的作用:洞察神经炎症和病毒发病机理。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105383
Veronika Pranclova , Lenka Nedvedova , Eliska Kotounova , Vaclav Hönig , Marketa Dvorakova , Marika Davidkova , Tomas Bily , Marie Vancova , Daniel Ruzek , Martin Palus
Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus responsible for severe infections of the central nervous system. Although neurons are predominantly targeted, specific involvement of microglia in pathogenesis of TBE is not yet fully understood. In this study, the susceptibility of human microglia to TBEV is investigated, focusing on productive infection and different immune responses of different viral strains. We investigated primary human microglia and two immortalized microglial cell lines exposed to three TBEV strains (Hypr, Neudörfl and 280), each differing in virulence. Our results show that all microglia cultures tested support long-term productive infections, regardless of the viral strain. In particular, immune response varied significantly with the viral strain, as shown by the differential secretion of cytokines and chemokines such as IP-10, MCP-1, IL-8 and IL-6, quantified using a Luminex 48-plex assay. The most virulent strain triggered the highest cytokine induction. Electron tomography revealed substantial ultrastructural changes in the infected microglia, despite the absence of cytopathic effects. These findings underscore the susceptibility of human microglia to TBEV and reveal strain-dependent variations in viral replication and immune responses, highlighting the complex role of microglia in TBEV-induced neuropathology and contribute to a deeper understanding of TBE pathogenesis and neuroinflammation.
蜱传脑炎病毒(TBEV)是一种具有神经侵袭性的正黄病毒,可导致中枢神经系统的严重感染。虽然蜱传脑炎病毒主要针对神经元,但小胶质细胞在蜱传脑炎发病机制中的具体参与尚未完全明了。本研究调查了人类小胶质细胞对 TBEV 的易感性,重点是不同病毒株的生产性感染和不同的免疫反应。我们研究了暴露于三种 TBEV 株系(Hypr、Neudörfl 和 280)的原代人类小胶质细胞和两种永生化小胶质细胞系,每种株系的毒性都不同。我们的研究结果表明,无论病毒毒株如何,所有测试过的小胶质细胞培养物都能支持长期的生产性感染。特别是,免疫反应随病毒株的不同而有显著差异,这体现在细胞因子和趋化因子(如 IP-10、MCP-1、IL-8 和 IL-6)的不同分泌量上。毒力最强的菌株引发的细胞因子诱导最高。电子断层扫描显示,尽管没有细胞病理效应,但受感染的小胶质细胞的超微结构发生了重大变化。这些发现强调了人类小胶质细胞对TBEV的易感性,并揭示了病毒复制和免疫反应的毒株依赖性变化,突出了小胶质细胞在TBEV诱导的神经病理学中的复杂作用,有助于加深对TBE发病机制和神经炎症的理解。
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引用次数: 0
Trypanosoma cruzi Vps34 colocalizes with Beclin1 and plays a role in parasite invasion of the host cell by modulating the expression of a sub-group of trans-sialidases 克氏锥虫 Vps34 与 Beclin1 共定位,通过调节反式苷酸酶亚群的表达,在寄生虫入侵宿主细胞的过程中发挥作用。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105385
Carlos Alcides Nájera , Mercedes Soares-Silva , Fernando Y. Maeda , Wanderson Duarte DaRocha , Isabela Meneghelli , Ana Clara Mendes , Marina Ferreira Batista , Claudio Vieira Silva , José Franco da Silveira , Cristina M. Orikaza , Nobuko Yoshida , Viviane Grazielle Silva , Santuza Maria Ribeiro Teixeira , Daniella Castanheira Bartholomeu , Diana Bahia
Trypanosoma cruzi, the etiological agent of Chagas' disease, can infect both phagocytic and non-phagocytic cells. T. cruzi gp82 and gp90 are cell surface proteins belonging to Group II trans-sialidases known to be involved in host cell binding and invasion. Phosphatidylinositol kinases (PIK) are lipid kinases that phosphorylate phospholipids in their substrates or in themselves, regulating important cellular functions such as metabolism, cell cycle and survival. Vps34, a class III PIK, regulates autophagy, trimeric G-protein signaling, and the mTOR (mammalian Target of Rapamycin) nutrient-sensing pathway. The mammalian autophagy gene Beclin1 interacts to Vps34 forming Beclin 1–Vps34 complexes involved in autophagy and protein sorting. In T. cruzi epimastigotes, (a non-infective replicative form), TcVps34 has been related to morphological and functional changes associated to vesicular trafficking, osmoregulation and receptor-mediated endocytosis. We aimed to characterize the role of TcVps34 during invasion of HeLa cells by metacyclic (MT) forms. MTs overexpressing TcVps34 showed lower invasion rates compared to controls, whilst exhibiting a significant decrease in gp82 expression in the parasite surface. In addition, we showed that T. cruzi Beclin (TcBeclin1) colocalizes with TcVps34 in epimastigotes, thus suggesting the formation of complexes that may play conserved cellular roles already described for other eukaryotes.
南美锥虫病的病原体克鲁兹锥虫既能感染吞噬细胞,也能感染非吞噬细胞。克鲁兹锥虫的 gp82 和 gp90 是细胞表面蛋白,属于已知参与宿主细胞结合和入侵的第二类反式裂解酶。磷脂酰肌醇激酶(PIK)是一种脂质激酶,能使其底物或本身的磷脂磷酸化,从而调节新陈代谢、细胞周期和存活等重要的细胞功能。Vps34 是第三类 PIK,调节自噬、三聚 G 蛋白信号传导和 mTOR(哺乳动物雷帕霉素靶标)营养传感途径。哺乳动物的自噬基因 Beclin1 与 Vps34 相互作用,形成 Beclin 1-Vps34 复合物,参与自噬和蛋白质分拣。在 T. cruzi 表皮原虫(一种非感染性复制形式)中,TcVps34 与囊泡运输、渗透调节和受体介导的内吞相关的形态和功能变化有关。我们的目的是鉴定 TcVps34 在元clic(MT)形式入侵 HeLa 细胞过程中的作用。与对照组相比,过量表达 TcVps34 的 MT 侵袭率较低,同时寄生虫表面的 gp82 表达量显著减少。此外,我们还发现 T. cruzi Beclin(TcBeclin1)与 TcVps34 共同定位在表皮原虫中,这表明形成的复合物可能在其他真核生物中发挥保守的细胞作用。
{"title":"Trypanosoma cruzi Vps34 colocalizes with Beclin1 and plays a role in parasite invasion of the host cell by modulating the expression of a sub-group of trans-sialidases","authors":"Carlos Alcides Nájera ,&nbsp;Mercedes Soares-Silva ,&nbsp;Fernando Y. Maeda ,&nbsp;Wanderson Duarte DaRocha ,&nbsp;Isabela Meneghelli ,&nbsp;Ana Clara Mendes ,&nbsp;Marina Ferreira Batista ,&nbsp;Claudio Vieira Silva ,&nbsp;José Franco da Silveira ,&nbsp;Cristina M. Orikaza ,&nbsp;Nobuko Yoshida ,&nbsp;Viviane Grazielle Silva ,&nbsp;Santuza Maria Ribeiro Teixeira ,&nbsp;Daniella Castanheira Bartholomeu ,&nbsp;Diana Bahia","doi":"10.1016/j.micinf.2024.105385","DOIUrl":"10.1016/j.micinf.2024.105385","url":null,"abstract":"<div><div><em>Trypanosoma cruzi</em>, the etiological agent of Chagas' disease, can infect both phagocytic and non-phagocytic cells. <em>T. cruzi</em> gp82 and gp90 are cell surface proteins belonging to Group II <em>trans</em>-sialidases known to be involved in host cell binding and invasion. Phosphatidylinositol kinases (PIK) are lipid kinases that phosphorylate phospholipids in their substrates or in themselves, regulating important cellular functions such as metabolism, cell cycle and survival. Vps34, a class III PIK, regulates autophagy, trimeric G-protein signaling, and the mTOR (mammalian Target of Rapamycin) nutrient-sensing pathway. The mammalian autophagy gene Beclin1 interacts to Vps34 forming Beclin 1–Vps34 complexes involved in autophagy and protein sorting. In <em>T. cruzi</em> epimastigotes, (a <em>non</em>-infective replicative form), TcVps34 has been related to morphological and functional changes associated to vesicular trafficking, osmoregulation and receptor-mediated endocytosis. We aimed to characterize the role of TcVps34 during invasion of HeLa cells by metacyclic (MT) forms. MTs overexpressing TcVps34 showed lower invasion rates compared to controls, whilst exhibiting a significant decrease in gp82 expression in the parasite surface. In addition, we showed that <em>T. cruzi</em> Beclin (TcBeclin1) colocalizes with TcVps34 in epimastigotes, thus suggesting the formation of complexes that may play conserved cellular roles already described for other eukaryotes.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105385"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Extracellular vesicles from primary human macrophages stimulated with VIP or PACAP mediate anti-SARS-CoV-2 activities in monocytes through NF-κB signaling pathway 受到 VIP 或 PACAP 刺激的原代人类巨噬细胞的细胞外囊泡通过 NF-κB 信号通路介导单核细胞的抗 SARS-CoV-2 活性。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105400
Luis A. Arteaga-Blanco , Jairo R. Temerozo , Lucas P.S. Tiné , Luíza Dantas-Pereira , Carolina Q. Sacramento , Natalia Fintelman-Rodrigues , Beatriz M. Toja , Suelen Silva Gomes Dias , Caroline S. de Freitas , Camila Couto Espírito-Santo , Ygor P. Silva , Rudimar L. Frozza , Patrícia T. Bozza , Rubem F.S. Menna-Barreto , Thiago Moreno L. Souza , Dumith Chequer Bou-Habib
Infection by SARS-CoV-2 is associated with uncontrolled inflammatory response during COVID-19 severe disease, in which monocytes are one of the main sources of pro-inflammatory mediators leading to acute respiratory distress syndrome. Extracellular vesicles (EVs) from different cells play important roles during SARS-CoV-2 infection, but investigations describing the involvement of EVs from primary human monocyte-derived macrophages (MDM) on the regulation of this infection are not available. Here, we describe the effects of EVs released by MDM stimulated with the neuropeptides VIP and PACAP on SARS-CoV-2-infected monocytes. MDM-derived EVs were isolated by differential centrifugation of medium collected from cells cultured for 24 h in serum-reduced conditions. Based on morphological properties, we distinguished two subpopulations of MDM-EVs, namely large (LEV) and small EVs (SEV). We found that MDM-derived EVs stimulated with the neuropeptides inhibited SARS-CoV-2 RNA synthesis/replication in monocytes, protected these cells from virus-induced cytopathic effects and reduced the production of pro-inflammatory mediators. In addition, EVs derived from VIP- and PACAP-treated MDM prevented the SARS-CoV-2-induced NF-κB activation. Overall, our findings suggest that MDM-EVs are endowed with immunoregulatory properties that might contribute to the antiviral and anti-inflammatory responses in SARS-CoV-2-infected monocytes and expand our knowledge of EV effects during COVID-19 pathogenesis.
SARS-CoV-2 感染与 COVID-19 严重疾病期间失控的炎症反应有关,其中单核细胞是导致急性呼吸窘迫综合征的促炎介质的主要来源之一。来自不同细胞的胞外囊泡(EVs)在 SARS-CoV-2 感染过程中发挥着重要作用,但目前还没有研究说明来自原代人类单核细胞衍生巨噬细胞(MDM)的 EVs 参与了这种感染的调控。在这里,我们描述了在神经肽 VIP 和 PACAP 的刺激下,MDM 释放的 EVs 对感染 SARS-CoV-2 的单核细胞的影响。通过对在血清还原条件下培养 24 小时的细胞所收集的培养基进行差速离心,分离出了 MDM 衍生的 EVs。根据形态学特性,我们区分了MDM-EVs的两个亚群,即大EVs(LEV)和小EVs(SEV)。我们发现,用神经肽刺激 MDM 衍生的 EVs 可抑制单核细胞中 SARS-CoV-2 RNA 的合成/复制,保护这些细胞免受病毒诱导的细胞病理效应的影响,并减少促炎介质的产生。此外,VIP 和 PACAP 处理过的 MDM 衍生的 EV 可防止 SARS-CoV-2 诱导的 NF-κB 激活。总之,我们的研究结果表明,MDM-EVs 具有免疫调节特性,可能有助于 SARS-CoV-2 感染单核细胞的抗病毒和抗炎反应,并扩展了我们对 COVID-19 发病过程中 EV 作用的认识。
{"title":"Extracellular vesicles from primary human macrophages stimulated with VIP or PACAP mediate anti-SARS-CoV-2 activities in monocytes through NF-κB signaling pathway","authors":"Luis A. Arteaga-Blanco ,&nbsp;Jairo R. Temerozo ,&nbsp;Lucas P.S. Tiné ,&nbsp;Luíza Dantas-Pereira ,&nbsp;Carolina Q. Sacramento ,&nbsp;Natalia Fintelman-Rodrigues ,&nbsp;Beatriz M. Toja ,&nbsp;Suelen Silva Gomes Dias ,&nbsp;Caroline S. de Freitas ,&nbsp;Camila Couto Espírito-Santo ,&nbsp;Ygor P. Silva ,&nbsp;Rudimar L. Frozza ,&nbsp;Patrícia T. Bozza ,&nbsp;Rubem F.S. Menna-Barreto ,&nbsp;Thiago Moreno L. Souza ,&nbsp;Dumith Chequer Bou-Habib","doi":"10.1016/j.micinf.2024.105400","DOIUrl":"10.1016/j.micinf.2024.105400","url":null,"abstract":"<div><div>Infection by SARS-CoV-2 is associated with uncontrolled inflammatory response during COVID-19 severe disease, in which monocytes are one of the main sources of pro-inflammatory mediators leading to acute respiratory distress syndrome. Extracellular vesicles (EVs) from different cells play important roles during SARS-CoV-2 infection, but investigations describing the involvement of EVs from primary human monocyte-derived macrophages (MDM) on the regulation of this infection are not available. Here, we describe the effects of EVs released by MDM stimulated with the neuropeptides VIP and PACAP on SARS-CoV-2-infected monocytes. MDM-derived EVs were isolated by differential centrifugation of medium collected from cells cultured for 24 h in serum-reduced conditions. Based on morphological properties, we distinguished two subpopulations of MDM-EVs, namely large (LEV) and small EVs (SEV). We found that MDM-derived EVs stimulated with the neuropeptides inhibited SARS-CoV-2 RNA synthesis/replication in monocytes, protected these cells from virus-induced cytopathic effects and reduced the production of pro-inflammatory mediators. In addition, EVs derived from VIP- and PACAP-treated MDM prevented the SARS-CoV-2-induced NF-κB activation. Overall, our findings suggest that MDM-EVs are endowed with immunoregulatory properties that might contribute to the antiviral and anti-inflammatory responses in SARS-CoV-2-infected monocytes and expand our knowledge of EV effects during COVID-19 pathogenesis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105400"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Characterization of novel HIV fusion-inhibitory lipopeptides with the M-T hook structure 具有 M-T 钩结构的新型 HIV 融合抑制脂肽的特征。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105366
Xiuzhu Geng , Xiaohui Ding , Yuanmei Zhu , Huihui Chong , Yuxian He
Combination antiretroviral therapy (cART) has significantly improved the survival of HIV-infected individuals, but long-term treatment can cause side-effects and drug resistance; thus, the development of new antivirals is of importance. We previously identified an M-T hook structure and accordingly designed short-peptide fusion inhibitor 2P23, which mainly targets the gp41 pocket site and displays potent, broad-spectrum anti-HIV activity. In this study, we continuingly characterized the amino acid sequences of peptide and lipopeptide-based inhibitors containing the M-T hook residues. Among a group of lipopeptides, stearic acid (C18)-modified LP-25 and LP-29 exhibited greatly improved inhibitions against divergent HIV-1 subtypes and drug-resistant mutants. LP-25 and LP-29 were evaluated in rhesus macaques, and the ex vivo inhibition data demonstrated their potent, long-lasting in vivo anti-HIV activity, with LP-25 much better than LP-29. Both the lipopeptides displayed high α-helicity, thermostability and binding ability to a target-mimic peptide, and they were metabolically stable when treated with high temperature, proteolytic enzymes, human or monkey sera and human liver microsomes. Therefore, our studies have provided critical information for understanding the structure-activity relationship of HIV fusion inhibitors with the M-T hook structure and offered novel candidates for drug development.
联合抗逆转录病毒疗法(cART)大大提高了艾滋病毒感染者的生存率,但长期治疗会产生副作用和耐药性;因此,开发新的抗病毒药物非常重要。我们之前确定了 M-T 钩结构,并据此设计了短肽融合抑制剂 2P23,它主要针对 gp41 口袋位点,具有强效、广谱的抗 HIV 活性。在这项研究中,我们继续对含有 M-T 钩残基的肽类和脂肽类抑制剂的氨基酸序列进行了表征。在一组脂肽中,经硬脂酸(C18)修饰的 LP-25 和 LP-29 对不同 HIV-1 亚型和耐药突变体的抑制作用大大提高。在猕猴体内对 LP-25 和 LP-29 进行了评估,其体内外抑制数据表明,它们具有强效、持久的体内抗 HIV 活性,其中 LP-25 的效果比 LP-29 更好。这两种脂肽都显示出很高的α-螺旋度、热稳定性和与目标模拟肽的结合能力,而且在高温、蛋白水解酶、人或猴血清和人肝微粒体的作用下,它们的代谢都很稳定。因此,我们的研究为理解具有 M-T 钩结构的 HIV 融合抑制剂的结构-活性关系提供了关键信息,并为药物开发提供了新的候选物。
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引用次数: 0
miR-190 restores the innate immune homeostasis of Drosophila by directly inhibiting Tab2 in Imd pathway miR-190 通过直接抑制 Imd 通路中的 Tab2 恢复果蝇的先天性免疫平衡。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105399
Xiaolong Yao , Yuqing He , Canhe Zhu , Shangmin Yang , Jing Wu , Fei Ma , Ping Jin
The Drosophila Imd pathways are well-known mechanisms involved in innate immunity responsible for Gram-negative (G-) bacterial infection. The intensity and durability of immunity need to be finely regulated to keep sufficient immune activation meanwhile avoid excessive immune response. In this study, we firstly demonstrated that miR-190 can downregulate the expression levels of antimicrobial peptides (AMPs) in the Imd immune pathway after Escherichia coli infection using the miR-190 overexpression flies and the miR-190KO/+ flies. Secondly, miR-190 overexpression significantly reduces while miR-190 KO increases Drosophila survival rates upon lethal Enterobacter cloacae infection. Thirdly, we further demonstrated that miR-190 negatively regulates innate immune responses by directly targeting both RA/RB and RC isoforms of Tab2. In addition, the dynamic expression pattern of AMPs (Dpt, AttA, CecA1), miR-190 and Tab2 in the wild-type flies reveals that miR-190 play an important role in Drosophila immune homeostasis restoration at the late stage of E. coli infection. Collectively, our study reveals that miR-190 can downregulate the expression of AMPs by targeting Tab2 and promote immune homeostasis restoration in Drosophila Imd pathway. Our study provides new insights into the regulatory mechanism of animal innate immune homeostasis.
果蝇的 Imd 通路是众所周知的先天免疫机制,负责革兰氏阴性(G-)细菌感染。免疫的强度和持久性需要精细调节,以保持足够的免疫激活,同时避免过度的免疫反应。本研究首先利用miR-190过表达蝇和miR-190KO/+蝇证实了miR-190能下调大肠杆菌感染后Imd免疫通路中抗菌肽(AMPs)的表达水平。其次,miR-190 过表达会显著降低果蝇在感染致命的肠杆菌后的存活率,而 miR-190 KO 则会提高果蝇的存活率。第三,我们进一步证明,miR-190 通过直接靶向 Tab2 的 RA/RB 和 RC 异构体,负向调节先天性免疫反应。此外,AMPs(Dpt、AttA、CecA1)、miR-190 和 Tab2 在野生型果蝇中的动态表达模式显示,miR-190 在大肠杆菌感染后期果蝇免疫平衡恢复中发挥着重要作用。总之,我们的研究揭示了 miR-190 可通过靶向 Tab2 下调 AMPs 的表达,促进果蝇 Imd 通路中免疫稳态的恢复。我们的研究为动物先天性免疫平衡的调控机制提供了新的见解。
{"title":"miR-190 restores the innate immune homeostasis of Drosophila by directly inhibiting Tab2 in Imd pathway","authors":"Xiaolong Yao ,&nbsp;Yuqing He ,&nbsp;Canhe Zhu ,&nbsp;Shangmin Yang ,&nbsp;Jing Wu ,&nbsp;Fei Ma ,&nbsp;Ping Jin","doi":"10.1016/j.micinf.2024.105399","DOIUrl":"10.1016/j.micinf.2024.105399","url":null,"abstract":"<div><div>The <em>Drosophila</em> Imd pathways are well-known mechanisms involved in innate immunity responsible for Gram-negative (G-) bacterial infection. The intensity and durability of immunity need to be finely regulated to keep sufficient immune activation meanwhile avoid excessive immune response. In this study, we firstly demonstrated that miR-190 can downregulate the expression levels of antimicrobial peptides (AMPs) in the Imd immune pathway after <em>Escherichia coli</em> infection using the miR-190 overexpression flies and the miR-190KO/+ flies. Secondly, miR-190 overexpression significantly reduces while miR-190 KO increases <em>Drosophila</em> survival rates upon lethal <em>Enterobacter cloacae</em> infection. Thirdly, we further demonstrated that miR-190 negatively regulates innate immune responses by directly targeting both RA/RB and RC isoforms of <em>Tab2.</em> In addition, the dynamic expression pattern of AMPs (<em>Dpt</em>, <em>AttA</em>, <em>CecA1</em>), <em>miR-190</em> and <em>Tab2</em> in the wild-type flies reveals that miR-190 play an important role in <em>Drosophila</em> immune homeostasis restoration at the late stage of <em>E. coli</em> infection. Collectively, our study reveals that miR-190 can downregulate the expression of AMPs by targeting <em>Tab2</em> and promote immune homeostasis restoration in <em>Drosophila</em> Imd pathway. Our study provides new insights into the regulatory mechanism of animal innate immune homeostasis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105399"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Conference report: the first bacterial genome sequencing pan-European network conference 会议报告:第一届泛欧细菌基因组测序网络会议。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.micinf.2024.105410
Zoja Germuskova , Elisa Sosa , Amaya Campillay Lagos , Hege Vangstein Aamot , Mathew A. Beale , Claire Bertelli , Jonas Björkmann , Natacha Couto , Lena Feige , Gilbert Greub , Erika Tång Hallbäck , Emma B. Hodcroft , Dag Harmsen , Laurent Jacob , Keith A. Jolley , Andre Kahles , Alison E. Mather , Richard A. Neher , Aitana Neves , Stefan Niemann , Adrian Egli
{"title":"Conference report: the first bacterial genome sequencing pan-European network conference","authors":"Zoja Germuskova ,&nbsp;Elisa Sosa ,&nbsp;Amaya Campillay Lagos ,&nbsp;Hege Vangstein Aamot ,&nbsp;Mathew A. Beale ,&nbsp;Claire Bertelli ,&nbsp;Jonas Björkmann ,&nbsp;Natacha Couto ,&nbsp;Lena Feige ,&nbsp;Gilbert Greub ,&nbsp;Erika Tång Hallbäck ,&nbsp;Emma B. Hodcroft ,&nbsp;Dag Harmsen ,&nbsp;Laurent Jacob ,&nbsp;Keith A. Jolley ,&nbsp;Andre Kahles ,&nbsp;Alison E. Mather ,&nbsp;Richard A. Neher ,&nbsp;Aitana Neves ,&nbsp;Stefan Niemann ,&nbsp;Adrian Egli","doi":"10.1016/j.micinf.2024.105410","DOIUrl":"10.1016/j.micinf.2024.105410","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105410"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Copyright page Elsevier 版权页面Elsevier
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/S1286-4579(24)00186-2
{"title":"Copyright page Elsevier","authors":"","doi":"10.1016/S1286-4579(24)00186-2","DOIUrl":"10.1016/S1286-4579(24)00186-2","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105444"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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Microbes and Infection
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