Microbes and Infection最新文献_第6页

Host–parasite interactions after in vitro infection of human macrophages by Leishmania major: Dual analysis of microRNA and mRNA profiles reveals regulation of key processes through time kinetics 利什曼原虫体外感染人巨噬细胞后宿主与寄生虫的相互作用：microRNA和mRNA谱的双重分析揭示了通过时间动力学调节关键过程。

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-05-01 DOI: 10.1016/j.micinf.2025.105502

Chiraz Atri , Ghada Mkannez , Hanène Attia , Rabiaa Manel Sghaier , Aymen Bali , Ali Ben-Cheikh , Imen Rabhi , Béatrice Regnault , David Piquemal , Kais Ghedira , Koussay Dellagi , Dhafer Laouini , Fatma Zahra Guerfali

Micro-RNAs are a class of small non-coding ribonucleic acids that concomitantly regulate the expression of tens to hundreds of genes. To reduce the host's defense, Leishmania parasites hijack the cellular functions of their macrophage's targets through gene expression regulation. Only few studies have attempted to correlate miRNAs and mRNAs expressions within the same samples in the context of cellular parasitism.

In this study, the profiling of human macrophages, in vitro infected by L. major parasites, was performed at both the mRNA transcriptomic level and the expression of a set of 365 miRNAs, and we correlated their expressions in search for a common molecular signature.

Both mRNA and miRNA profiles were monitored during the first 24 h post-infection to capture potential time-dependent fluctuations. We then cross-correlated the cellular biological processes and the pathways associated to the predicted targets of miRNAs and to the differentially expressed mRNAs at all time points of infection on the same samples.

Besides revealing the classical activation of immune signaling pathways, the mRNA-micro-RNAs correlation study highlighted other common regulatory inflammatory biological processes, allowing identification of rapidly modulated pathways, and bringing further evidence on the early molecular cross talk that take place between Leishmania and infected cells.

微rna是一类小的非编码核糖核酸，同时调节数十到数百个基因的表达。为了降低宿主的防御，利什曼原虫通过基因表达调控来劫持巨噬细胞靶细胞的功能。只有少数研究试图在细胞寄生的背景下将相同样本中的mirna和mrna表达联系起来。本研究对体外感染L. major寄生虫的人巨噬细胞进行了mRNA转录组水平和一组365个mirna的表达分析，并将它们的表达进行了关联，以寻找共同的分子特征。在感染后的最初24小时内监测mRNA和miRNA谱，以捕获潜在的时间依赖性波动。然后，我们交叉关联了细胞生物学过程和与mirna预测靶标相关的途径，以及在同一样本感染的所有时间点上差异表达的mrna。除了揭示经典的免疫信号通路激活外，mRNA-micro-RNAs相关研究还强调了其他常见的调节炎症生物学过程，允许识别快速调节的途径，并为利什曼原虫和感染细胞之间发生的早期分子串扰提供进一步的证据。

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引用次数: 0

No association between anti-cytomegalovirus seropositivity and arthritis: evidence from the cross-sectional epidemiology and genetic association analyses 抗巨细胞病毒血清阳性与关节炎之间无关联：来自横断面流行病学和遗传关联分析的证据。

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-05-01 DOI: 10.1016/j.micinf.2025.105529

Changzhou Feng , Haining Li , Ying Zhou, Chu Zhang, Jin Yang, Haiqing Wang

Human cytomegalovirus (CMV), a β-herpesvirus associated with chronic inflammation and lifelong latency, has been implicated in the pathogenesis of arthritis. However, the nature of this relationship remains controversial. In this study, we integrate cross-sectional epidemiology analyses, genetic correlation assessments, and Mendelian randomization (MR) approaches to elucidate the potential association between CMV infection and arthritis-related conditions. Observational analysis of 5133 participants from the NHANES database revealed a positive association between CMV IgG seropositivity and arthritis (OR: 1.24; 95 % CI: 1.03–1.48; P = 0.02), particularly with the rheumatoid arthritis (RA) subtype (OR: 1.94; 95 % CI: 1.21–3.12; P < 0.01). However, these associations lost statistical significance after adjustment for multiple covariates (all P > 0.05). Subgroup and interaction analyses across different demographic and clinical subpopulations further confirmed the absence of these associations. Similarly, subtype analyses indicated no significant association between CMV IgG seropositivity and osteoarthritis (OA), other-arthritis, or unknown-arthritis, even before covariate adjustment. Linkage disequilibrium score regression (LDSC) analysis did not reveal a significant genetic correlation between anti-CMV IgG levels and arthritis, including RA and OA (all P > 0.05), suggesting no shared genetic basis. Furthermore, bidirectional MR analyses found no evidence of a causal relationship between CMV antibody responses—including IgG and three CMV-related peptide antigens (pp28, pp52, and pp150)—and arthritis, RA, or OA (all P > 0.05). Collectively, these findings suggest that previously reported positive associations between CMV seropositivity and arthritis may have been confounded by other covariates rather than reflecting a true causal relationship.

人巨细胞病毒（CMV）是一种与慢性炎症和终身潜伏期相关的β-疱疹病毒，与关节炎的发病机制有关。然而，这种关系的性质仍然存在争议。在这项研究中，我们整合了横断面流行病学分析、遗传相关性评估和孟德尔随机化（MR）方法来阐明巨细胞病毒感染与关节炎相关疾病之间的潜在关联。来自NHANES数据库的5133名参与者的观察性分析显示CMV IgG血清阳性与关节炎呈正相关(OR: 1.24；95% ci: 1.03-1.48；P = 0.02)，特别是类风湿关节炎（RA）亚型(OR: 1.94；95% ci: 1.21-3.12；P < 0.01)。然而，在多协变量调整后，这些关联失去了统计学意义（均P < 0.05）。跨不同人口统计学和临床亚群的亚组和相互作用分析进一步证实了这些关联的缺失。同样，亚型分析显示，即使在协变量调整之前，CMV IgG血清阳性与骨关节炎（OA）、其他关节炎或未知关节炎之间也没有显着关联。连锁不平衡评分回归（LDSC）分析显示抗巨细胞病毒IgG水平与关节炎（包括RA和OA）没有显著的遗传相关性（P < 0.05），提示没有共同的遗传基础。此外，双向MR分析未发现巨细胞病毒抗体反应（包括IgG和三种巨细胞病毒相关肽抗原（pp28、pp52和pp150））与关节炎、RA或OA之间存在因果关系的证据（P < 0.05）。总的来说，这些发现表明先前报道的巨细胞病毒血清阳性与关节炎之间的正相关可能被其他协变量混淆，而不是反映真正的因果关系。

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引用次数: 0

Chlamydia trachomatis regulates ferroptosis through the p53/SLC7A11 pathway to promote reproduction 沙眼衣原体通过p53/SLC7A11通路调控铁下垂，促进生殖。

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-05-01 DOI: 10.1016/j.micinf.2025.105505

Xinglv Wang , Chengyu Tang , Hongrong Wu , Jingrong Zhang , Lili Chen , Zhongyu Li

Genital tract Chlamydia trachomatis (Ct) infection is one of the most prevalent sexually transmitted infections (STIs) worldwide. However, its clinical progression is often insidious and prolonged. Understanding the mechanisms by which Ct influences cell death pathways is crucial for elucidating the pathogenic processes of this intracellular bacterium. Ferroptosis, a newly identified form of programmed cell death, is characterized by the iron-dependent accumulation of lipid peroxides. Despite its relevance, the interaction between Ct and ferroptosis remains poorly studied. In the present study, we first performed bioinformatics analysis based on RNA sequencing data under an in vitro model of Ct acute infection. Bioinformatics analysis revealed significant enrichment of differentially expressed genes in ferroptosis and p53 signaling pathways. Subsequently, we validated the hypothesis that Ct inhibits host ferroptosis by expression assays of ferroptosis-related proteins. Further cell proliferation, intracellular ferrous iron fluorescence, and lipid peroxidation assays multifaceted observations of the phenotype. Mechanistically, we found that Ct inhibition of ferroptosis acts by regulating the host p53/SLC7A11 pathway. Finally, indirect immunofluorescence assays demonstrated that ferroptosis decreases inclusion forming units (IFUs) of Ct progeny and thus affects its reproduction, which partly explains Ct's survival strategy of resisting host ferroptosis.

沙眼衣原体（Ct）感染是世界范围内最普遍的性传播感染之一。然而，其临床进展往往是潜伏的和长期的。了解Ct影响细胞死亡途径的机制对于阐明这种细胞内细菌的致病过程至关重要。铁死亡是一种新发现的程序性细胞死亡形式，其特点是脂质过氧化物的铁依赖性积累。尽管其相关性，Ct和铁下垂之间的相互作用仍然很少研究。在本研究中，我们首先在体外Ct急性感染模型下进行了基于RNA测序数据的生物信息学分析。生物信息学分析显示，铁下垂和p53信号通路中差异表达基因显著富集。随后，我们通过对铁沉相关蛋白的表达分析验证了Ct抑制宿主铁沉的假设。进一步的细胞增殖，细胞内亚铁荧光和脂质过氧化分析，多方面观察表型。在机制上，我们发现Ct抑制铁下垂是通过调节宿主p53/SLC7A11途径起作用的。最后，间接免疫荧光分析表明，铁下垂降低了Ct后代的包涵体形成单位（IFUs），从而影响其繁殖，这在一定程度上解释了Ct抵抗宿主铁下垂的生存策略。

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引用次数: 0

Comparative pathoadaptation of Mycobacterium canettii and Mycobacterium tuberculosis: Insights from assays on phagosome acidification, cytosolic access, and transcriptomics canettii分枝杆菌和结核分枝杆菌的比较病理适应：从吞噬体酸化、细胞质通路和转录组学分析的见解。

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-05-01 DOI: 10.1016/j.micinf.2025.105503

Camila do Nascimento Araujo, Felipe Silva, Cristina Kraemer Zimpel , Taiana Tainá Silva-Pereira, Naila Cristina Soler-Camargo, Filipe Menegatti de Melo , Marcelo Valdemir de Araújo , Ana Marcia de Sá Guimarães

Genetic and molecular differences between Mycobacterium tuberculosis (Mtb) and its ancestral counterpart, Mycobacterium canettii (Mcan), remain poorly known. Our study aimed to compare their modulation of phagosome acidification and cytosolic access in macrophages, and their in vitro transcriptomes. Using spectrofluorometry, we tracked pH changes in mycobacteria-containing vacuoles in THP-1 macrophages. A single-cell FRET protocol evaluated cytosolic access of mycobacteria in these cells. Similar to Mtb, Mcan inhibits phagosome acidification and accesses the cytosol. Transcriptomic and genetic analyses reveal mutations in two-component systems (PhoPR, SenX3-RegX3, and DevRS/DosRS) and in specific genes (e.g., lactate dehydrogenase and espACD) driving variations in gene expression between pathogens. Moreover, Mcan upregulates genes of iron and molybdopterin metabolism compared to Mtb, suggesting a role for metals in the evolution of tuberculous mycobacteria. The upregulation of the termination factor Rho in Mtb also suggests differences in antisense transcription and/or gene expression regulation. In conclusion, phagosome modulation and cytosolic access in macrophages are ancestral traits predating the emergence of the MTBC and not exclusive to Mtb's strict pathogenic lifestyle. Additionally, gene expression regulation likely shaped the phenotypic differences between Mcan and Mtb, contributing to the evolutionary transition from an environmental Mcan-like ancestor to the MTBC's host-adapted lifestyle.

结核分枝杆菌（Mtb）与其祖先对应的卡内蒂分枝杆菌（Mcan）之间的遗传和分子差异仍然知之甚少。我们的研究旨在比较它们对巨噬细胞吞噬体酸化和细胞质通路的调节，以及它们的体外转录组。利用荧光光谱法，我们追踪了THP-1巨噬细胞中含有分枝杆菌的液泡的pH变化。单细胞FRET方案评估了分枝杆菌在这些细胞中的细胞质通路。与Mtb类似，Mcan抑制吞噬体酸化并进入细胞质。转录组学和遗传学分析揭示了双组分系统（PhoPR、SenX3-RegX3和DevRS/DosRS）和特定基因（如乳酸脱氢酶和espACD）的突变驱动病原体之间基因表达的变化。此外，与Mtb相比，Mcan上调了铁和钼酸盐代谢基因，这表明金属在结核分枝杆菌的进化中发挥了作用。Mtb中终止因子Rho的上调也提示了反义转录和/或基因表达调控的差异。总之，巨噬细胞中的吞噬体调节和细胞质通路是MTBC出现之前的祖先特征，而不是Mtb严格的致病生活方式所独有的。此外，基因表达调控可能塑造了Mcan和Mtb之间的表型差异，促进了从环境类Mcan祖先到MTBC适应宿主生活方式的进化转变。

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引用次数: 0

Pseudomonas aeruginosa-derived DnaJ induces TLR2 expression through TLR10-mediated activation of the PI3K-SGK1 pathway in macrophages 铜绿假单胞菌衍生的DnaJ通过tlr10介导的巨噬细胞PI3K-SGK1通路激活诱导TLR2表达。

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-05-01 DOI: 10.1016/j.micinf.2025.105481

Jaehoo Lee , Yongxin Jin , Weihui Wu , Yeji Lee , Un-Hwan Ha

TLR2 is a key component of the innate immune system, responsible for recognizing Gram-positive bacterial components and initiating inflammatory signaling cascades that activate defense responses. However, little is known about the regulatory effects of Pseudomonas aeruginosa (P. aeruginosa) on TLR2 expression. In this study, we investigated the potential link between P. aeruginosa-derived DnaJ and TLR2 expression in macrophages, as well as the activation of downstream signaling pathways. Our findings revealed that DnaJ significantly induced TLR2 expression in a dose- and time-dependent manner, predominantly affecting TLR2 with minimal impact on other TLRs, such as TLR4 and TLR5, which detect bacterial PAMPs. The DnaJ-mediated TLR2 induction was driven by activation of the PI3K-SGK1 signaling pathway, with TLR10 playing a crucial role in facilitating these effects. This increase in TLR2 expression led to enhanced production of inflammatory cytokines in response to secondary Staphylococcus aureus infections, indicating a role in boosting host defense mechanisms. In conclusion, these findings suggest that P. aeruginosa-derived DnaJ promotes TLR2 expression via TLR10-mediated activation of the PI3K-SGK1 pathway, thereby enhancing host immune responses against Gram-positive bacterial infections.

TLR2是先天免疫系统的关键组成部分，负责识别革兰氏阳性细菌成分并启动炎症信号级联反应，激活防御反应。然而，关于铜绿假单胞菌对TLR2表达的调控作用，目前所知甚少。在这项研究中，我们研究了P. aeruginosa衍生的DnaJ与巨噬细胞中TLR2表达之间的潜在联系，以及下游信号通路的激活。我们的研究结果显示，DnaJ以剂量和时间依赖的方式显著诱导TLR2表达，主要影响TLR2，对其他tlr（如检测细菌PAMPs的TLR4和TLR5）的影响最小。dnaj介导的TLR2诱导是由PI3K-SGK1信号通路的激活驱动的，TLR10在促进这些作用中起着至关重要的作用。TLR2表达的增加导致继发性金黄色葡萄球菌感染时炎症细胞因子的产生增加，表明其在增强宿主防御机制中起作用。综上所述，这些发现表明P. aeruginosa来源的DnaJ通过tlr10介导的PI3K-SGK1通路激活促进TLR2表达，从而增强宿主对革兰氏阳性细菌感染的免疫应答。

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引用次数: 0

Nano-enhanced benzylpenicillin: Bridging antibacterial action with anti-inflammatory potential against antibiotic-resistant bacteria 纳米增强型苄青霉素：抗生素耐药细菌的抗菌作用与消炎潜力的桥梁

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-03-01 DOI: 10.1016/j.micinf.2024.105436

Natália Cristina Gomes-da-Silva , Álefe Roger Silva França , Clenilton Costa dos Santos , Luciana Magalhães Rebelo Alencar , Elaine Cruz Rosas , Luana Barbosa Corrêa , Carolline M.A. Lorentino , André L.S. Santos , Eduardo Ricci-Junior , Ralph Santos-Oliveira

This study investigates the enhancement of benzylpenicillin's antibacterial properties using nanomedicine, specifically by developing benzylpenicillin nanoemulsions. To address the escalating issue of bacterial resistance, we employed the advanced techniques Raman spectroscopy and atomic force microscopy to analyze the nanoemulsions' molecular structure and characteristics. We then evaluated the impact of these nanoemulsions on nitric oxide production by macrophages to deternine their potential to modulate inflammatory responses. We further assessed the antibacterial effectiveness of the nanoparticles against the pathogens Streptococcus pyogenes (Group A Streptococcus) and Streptococcus agalactiae (Group B Streptococcus). The results of antibiograms showed significant efficacy against Gram-positive bacteria, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, confirming their bactericidal potential. The investigation into the mechanism of action suggested substantial disruption to bacterial membrane integrity, underscoring a possible mode of antibacterial activity. Overall, the study provides valuable insights into the synergistic relationship between antibiotics and nanoparticles. In particular, it demonstrates the potential of benzylpenicillin nanoparticles to enhance the antimicrobial efficacy and influence inflammatory responses obtained by evaluating nitrite, IL-6 and TNF-α, offering promising avenues for future clinical applications and strategies to combat bacterial resistance.

本研究探讨了利用纳米药物，特别是通过开发苄青霉素纳米乳剂来增强苄青霉素的抗菌特性。为了解决不断升级的细菌耐药性问题，我们采用了先进的拉曼光谱和原子力显微镜技术来分析纳米乳剂的分子结构和特性。然后，我们评估了这些纳米乳剂对巨噬细胞产生一氧化氮的影响，以确定其调节炎症反应的潜力。我们进一步评估了纳米颗粒对化脓性链球菌（A 组链球菌）和无乳链球菌（B 组链球菌）的抗菌效果。抗生素图谱的结果表明，它们对革兰氏阳性细菌有显著疗效，最低抑菌浓度（MIC）和最低杀菌浓度（MBC）值证实了它们的杀菌潜力。对其作用机制的研究表明，它们能极大地破坏细菌膜的完整性，从而强调了一种可能的抗菌活性模式。总之，这项研究为了解抗生素与纳米粒子之间的协同作用关系提供了宝贵的见解。特别是，它证明了苄青霉素纳米粒子具有增强抗菌效力和影响炎症反应（通过评估亚硝酸盐、IL-6 和 TNF-α）的潜力，为未来的临床应用和抗击细菌耐药性的策略提供了前景广阔的途径。

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引用次数: 0

Photodynamic therapy reduces viability, enhances itraconazole activity, and impairs mitochondrial physiology of Sporothrix brasiliensis 光动力疗法降低了巴西孢子虫的活力，增强了伊曲康唑的活性，并损害了线粒体的生理机能。

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-03-01 DOI: 10.1016/j.micinf.2024.105440

Mariana Lucy Mesquita Ramos , Azuil Barrinha , Glauber Ribeiro de Sousa Araújo , Vinicius Alves , Iara Bastos de Andrade , Dario Corrêa-Junior , Maria Cristina Machado Motta , Rodrigo Almeida-Paes , Susana Frases

Sporothrix brasiliensis is the main agent of sporotrichosis in Brazil, with few therapeutic options. This study aimed to investigate the in vitro efficacy of photodynamic therapy using a diode laser (InGaAIP) in combination with the photosensitizer methylene blue against S. brasiliensis yeasts. Additionally, we evaluated the underexplored mitochondrial activity of S. brasiliensis and the impact of laser treatment on the fungal mitochondrial aspects post-treatment. Three strains of S. brasiliensis were used, including a non-wild-type strain to itraconazole. Yeast viability was determined by counting colony-forming units. For a comprehensive analysis of irradiated versus non-irradiated cells, we assessed combined therapy with itraconazole, scanning electron microscopy of cells, and mitochondrial activity. The latter included high-resolution respirometry, membrane potential analysis, and reactive oxygen species production. Methylene blue combined with photodynamic therapy inhibited the growth of the isolates, including the non-wild-type strain to itraconazole. Photodynamic therapy induced the production of reactive oxygen species, which negatively affected mitochondrial function, resulting in decreased membrane potential and cell death. Photodynamic therapy altered the ultrastructure and mitochondrial physiology of S. brasiliensis, suggesting a new therapeutic approach for sporotrichosis caused by this species.

巴西孢子丝菌（Sporothrix brasiliensis）是巴西孢子丝菌病的主要病原体，治疗方法很少。本研究旨在探讨使用二极管激光器（InGaAIP）结合光敏剂亚甲基蓝对巴西孢子丝菌酵母进行光动力疗法的体外疗效。此外，我们还评估了尚未充分探索的巴西酵母菌线粒体活性以及激光治疗对治疗后真菌线粒体方面的影响。我们使用了三种 S. brasiliensis 菌株，包括一种对伊曲康唑不耐受的非野生型菌株。通过计数菌落形成单位来确定酵母的活力。为了全面分析辐照与非辐照细胞，我们评估了伊曲康唑联合疗法、细胞扫描电子显微镜和线粒体活性。后者包括高分辨率呼吸测定、膜电位分析和活性氧生成。亚甲蓝与光动力疗法相结合抑制了分离菌株的生长，包括对伊曲康唑的非野生型菌株。光动力疗法诱导产生活性氧，对线粒体功能产生负面影响，导致膜电位降低和细胞死亡。光动力疗法改变了巴西孢子虫的超微结构和线粒体生理机能，为治疗该物种引起的孢子丝虫病提供了一种新的治疗方法。

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引用次数: 0

Production of a monoclonal antibody targeting the SARS-CoV-2 Omicron spike protein and analysis of SARS-CoV-2 Omicron mutations related to monoclonal antibody resistance 生产针对 SARS-CoV-2 Omicron 穗蛋白的单克隆抗体，分析与单克隆抗体抗性有关的 SARS-CoV-2 Omicron 突变。

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-03-01 DOI: 10.1016/j.micinf.2024.105461

Jinsoo Kim , Suyeon Kim , Sangkyu Park , Dongbum Kim , Minyoung Kim , Kyeongbin Baek , Bo Min Kang , Ha-Eun Shin , Myeong-Heon Lee , Younghee Lee , Hyung-Joo Kwon

SARS-CoV-2 mutations have resulted in the emergence of multiple concerning variants, with Omicron being the dominant strain presently. Therefore, we developed a monoclonal antibody (mAb) against the spike (S) protein of SARS-CoV-2 Omicron for therapeutic applications. We established the 1E3H12 mAb, recognizing the receptor binding domain (RBD) of the Omicron S protein, and found that the 1E3H12 mAb can efficiently recognize the Omicron S protein with weak affinity to the Alpha, Beta, and Mu variants, but not to the parental strain and Delta variant. Based on in vitro assays, the mAb demonstrated neutralizing activity against Omicron BA.1, BA.4/5, BQ.1.1, and XBB. A humanized antibody was further produced and proved to have neutralizing activity. To verify the potential limitations of the 1E3H12 mAb due to viral escape of SARS-CoV-2 Omicron variants, we analyzed the emergence of variants by whole genome deep sequencing after serial passage in cell culture. The results showed a few unique S protein mutations in the genome associated with resistance to the mAb. These findings suggest that this antibody not only contributes to the therapeutic arsenal against COVID-19 but also addresses the ongoing challenge of antibody resistance among the evolving subvariants of SARS-CoV-2 Omicron.

SARS-CoV-2 基因突变导致了多种有关变异株的出现，其中 Omicron 是目前的优势变异株。因此，我们开发了一种针对 SARS-CoV-2 Omicron 的尖峰（S）蛋白的单克隆抗体（mAb），用于治疗。我们建立了 1E3H12 mAb，它能识别 Omicron S 蛋白的受体结合域（RBD），并发现 1E3H12 mAb 能有效识别 Omicron S 蛋白，对 Alpha、Beta 和 Mu 变种有弱亲和力，但对亲本株和 Delta 变种没有亲和力。根据体外试验，该 mAb 对 Omicron BA.1、BA.4/5、BQ.1.1 和 XBB 具有中和活性。进一步生产的人源化抗体也被证明具有中和活性。为了验证 1E3H12 mAb 因 SARS-CoV-2 Omicron 变体的病毒逃逸而可能存在的局限性，我们通过全基因组深度测序分析了在细胞培养中连续培养后出现的变体。结果显示，基因组中有一些独特的 S 蛋白突变与对 mAb 的耐药性有关。这些研究结果表明，该抗体不仅有助于COVID-19的治疗，而且还能解决SARS-CoV-2 Omicron不断演变的亚变异体对抗体产生耐药性这一难题。

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引用次数: 0

Copyright page Elsevier 版权页面Elsevier

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-03-01 DOI: 10.1016/S1286-4579(25)00057-7

引用次数: 0

Intranasal immunization with poly I:C and CpG ODN adjuvants enhances the protective efficacy against Helicobacter pylori infection in mice 使用聚 I:C 和 CpG ODN 佐剂进行鼻内免疫可增强小鼠对幽门螺旋杆菌感染的保护效力。

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection

Pub Date : 2025-03-01 DOI: 10.1016/j.micinf.2024.105433

Min Sun, Yu Liu, Xiumei Ni, Runqing Tan, Yi Wang, Yajun Jiang, Dingxin Ke, Han Du, Gang Guo, Kaiyun Liu

Helicobacter pylori (H. pylori) infection is a serious public health issue, and development of vaccines is a desirable preventive strategy for H. pylori. Toll-like receptor (TLR) ligands have shown potential as vaccine adjuvants that induce immune responses, but polyinosinic-polycytidylic acid (poly I:C), a nucleic acid-based TLR9 ligand, is less well studied in H. pylori vaccine research. Here, we evaluated the effects of poly I:C and CpG oligodeoxynucleotide (CpG ODN), a nucleic acid TLR3 ligand, as adjuvants in combination with the H. pylori recombinant proteins LpoB and UreA to protect against H. pylori infection. For analysis of specific immune responses, the levels of specific antibodies and splenic cytokines were measured in the immunized mice. Compared with CpG ODN, poly I:C could induce mucosal sIgA antibody responses and reduce H. pylori colonization. Additionally, the combination of poly I:C and CpG ODN caused greater immunoprotection and significantly reduced gastritis, exerting synergistic effects. Analysis of splenic cytokines revealed that poly I:C mainly triggered a mixed Th1/Th2/Th17 immune response, whereas the combination of CpG ODN and poly I:C induced a Th1/Th17 immune response. Our findings indicated that increased levels of mucosal sIgA antibodies and a robust splenic Th1/Th17 immune response were associated with reduced H. pylori colonization in vaccinated mice. This study identified a potential TLR ligand adjuvant for developing more effective H. pylori vaccines.

幽门螺杆菌（H. pylori）感染是一个严重的公共卫生问题，开发疫苗是预防幽门螺杆菌感染的理想策略。Toll样受体（TLR）配体已显示出作为疫苗佐剂诱导免疫反应的潜力，但聚肌苷酸-聚胞苷酸（poly I:C）这种基于核酸的TLR9配体在幽门螺杆菌疫苗研究中的研究较少。在这里，我们评估了聚 I:C 和核酸 TLR3 配体 CpG 寡脱氧核苷酸（CpG ODN）作为佐剂与幽门螺杆菌重组蛋白 LpoB 和 UreA 结合使用对预防幽门螺杆菌感染的效果。为了分析特异性免疫反应，测量了免疫小鼠体内特异性抗体和脾细胞因子的水平。与 CpG ODN 相比，多聚 I:C 可诱导粘膜 sIgA 抗体反应，减少幽门螺杆菌定植。此外，多聚 I:C 和 CpG ODN 的组合能产生更强的免疫保护作用，并能显著减轻胃炎，发挥协同效应。对脾脏细胞因子的分析表明，多聚 I:C 主要引发 Th1/Th2/Th17 混合免疫反应，而 CpG ODN 和多聚 I:C 的组合则诱导 Th1/Th17 免疫反应。我们的研究结果表明，粘膜 sIgA 抗体水平的提高和脾脏 Th1/Th17 免疫反应的增强与接种疫苗的小鼠幽门螺杆菌定植率的降低有关。这项研究为开发更有效的幽门螺杆菌疫苗找到了一种潜在的 TLR 配体佐剂。

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