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Simulating the clinical manifestations and disease progression of human sepsis: A monobacterial injection approach for animal modeling. 模拟人类败血症的临床表现和疾病进展:动物模型的单菌注射法
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-01 DOI: 10.1080/21505594.2024.2395835
Xuanwen Ru, Simiao Chen, Danlei Chen, Qingyi Shao, Wenxia Shao, Qing Ye

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with great clinical heterogeneity, high morbidity, and high mortality. At the same time, there are many kinds of infection sources, the pathophysiology is very complex, and the pathogenesis has not been fully elucidated. An ideal animal model of sepsis can accurately simulate clinical sepsis and promote the development of sepsis-related pathogenesis, treatment methods, and prognosis. The existing sepsis model still uses the previous Sepsis 2.0 modelling standard, which has some problems, such as many kinds of infection sources, poor repeatability, inability to take into account single-factor studies, and large differences from clinical sepsis patients. To solve these problems, this study established a new animal model of sepsis. The model uses intravenous tail injection of a single bacterial strain, simplifying the complexity of multibacterial infection, and effectively solving the above problems.

败血症是指宿主对感染的反应失调而引起的危及生命的器官功能障碍,具有临床异质性大、发病率高、死亡率高等特点。同时,感染源种类繁多,病理生理学非常复杂,发病机制尚未完全阐明。理想的败血症动物模型可以准确模拟临床败血症,促进败血症相关发病机制、治疗方法和预后的发展。现有的脓毒症模型仍沿用之前的脓毒症 2.0 建模标准,存在感染源种类多、可重复性差、无法考虑单因素研究、与临床脓毒症患者差异大等问题。为了解决这些问题,本研究建立了一种新的败血症动物模型。该模型采用尾部静脉注射单一细菌菌株的方法,简化了多菌感染的复杂性,有效解决了上述问题。
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引用次数: 0
N-acetylcysteine promotes doxycycline resistance in the bacterial pathogen Edwardsiella tarda. 乙酰半胱氨酸可促进细菌病原体埃德温斯氏菌对强力霉素的耐药性。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-17 DOI: 10.1080/21505594.2024.2399983
Juan Guo, Qingqiang Xu, Yilin Zhong, Yubin Su

Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on Edwardsiella tarda ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of E. tarda to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in E. tarda, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying E. tarda resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.

细菌耐药性对人类和动物健康都构成了重大威胁。作为消炎药使用的 N-乙酰半胱氨酸(NAC)已被证明对细菌耐药性有不同的、截然不同的影响。然而,NAC 与细菌耐药性之间关系的确切机制仍不清楚,需要进一步研究。在本研究中,我们研究了 NAC 对细菌耐药性的影响及其内在机制。具体来说,我们研究了 NAC 对 Edwardsiella tarda ATCC15947(一种对多种抗生素具有耐药性的病原体)的影响。我们发现,NAC 可以促进 E. tarda 对多西环素等多种抗生素产生耐药性,从而提高细菌的存活率。通过蛋白质组分析,我们证明 NAC 能激活 E. tarda 的氨基酸代谢途径,从而提高细胞内谷胱甘肽(GSH)水平并减少活性氧(ROS)。此外,NAC 还能减少抗生素的流入,同时促进其流出,从而维持较低的细胞内抗生素浓度。我们还提出,NAC 可促进蛋白质聚集,从而产生抗生素耐药性。我们的研究描述了E. tarda对强力霉素产生耐药性的机制,并提醒人们不要滥用代谢物佐剂。
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引用次数: 0
Humoral responses to multiple SARS-CoV-2 variants after two doses of vaccine in kidney transplant patients. 肾移植患者接种两剂疫苗后对多种 SARS-CoV-2 变体的体液反应。
IF 5.2 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-08 DOI: 10.1080/21505594.2024.2351266
Pin-Xian Du, Shen-Shin Chang, Tzong-Shiann Ho, Hsi-Chang Shih, Pei-Shan Tsai, Guan-Da Syu

Background: The COVID-19 pandemic has led to millions of fatalities globally. Kidney transplant (KT) patients, given their comorbidities and under immunosuppressant drugs, are identified as a high-risk group. Though vaccination remains pivotal for pandemic control, some studies indicate that KT exhibits diminished immune reactions to SARS-CoV-2 vaccines. Therefore, evaluating the vaccine responses in KT, especially the humoral responses against emergent variants is crucial.Methods: We developed a multiplexed SARS-CoV-2 variant protein microarray, incorporating the extracellular domain (ECD) and the receptor binding domain (RBD) of the spike proteins from the variants. This was employed to investigate the collective humoral responses after administering two doses of mRNA-1273 and AZD1222 vaccines in KT under immunosuppressive drugs and in healthy controls.Results: After two doses of either mRNA-1273 or AZD1222, the KT generally showed lower surrogate neutralizing and total antibodies against spike ECD in multiple variants compared to healthy controls. Although two doses of mRNA-1273 induced 1.5-2 fold more surrogate neutralizing and total antibodies than AZD1222 in healthy controls, the KT subjects with two doses of mRNA-1273 generally exhibited higher surrogate neutralizing but similar total antibodies against spike ECD in multiple variants. There were moderate to high correlations between the surrogate neutralizing and total antibodies against spike ECDs.Conclusion: This study offers pivotal insights into the relative vulnerability of KT concerning humoral immunity and the evolving mutations of SARS-CoV-2. Such findings are useful for evaluating vaccine responses and recommending vaccine episodes for KT.

背景:COVID-19 大流行已导致全球数百万人死亡。肾移植(KT)患者因其合并症和服用免疫抑制剂而被确定为高危人群。尽管疫苗接种仍是控制大流行病的关键,但一些研究表明,KT 对 SARS-CoV-2 疫苗的免疫反应较弱。因此,评估 KT 对疫苗的反应,尤其是对新出现变种的体液反应至关重要:方法:我们开发了一种多重 SARS-CoV-2 变体蛋白芯片,其中包含变体尖峰蛋白的胞外结构域 (ECD) 和受体结合结构域 (RBD)。结果发现,在服用免疫抑制药物的 KT 和健康对照组中接种两剂 mRNA-1273 和 AZD1222 疫苗后,体液反应集体发生变化:结果:与健康对照组相比,在接种两剂 mRNA-1273 或 AZD1222 疫苗后,KT 普遍表现出较低的针对多变体尖头 ECD 的替代中和抗体和总抗体。虽然在健康对照组中,两剂mRNA-1273诱导的代偿中和抗体和总抗体比AZD1222高1.5-2倍,但在服用两剂mRNA-1273后,KT受试者在多个变体中普遍表现出较高的代偿中和抗体,但针对尖峰ECD的总抗体与之相似。代偿中和抗体与针对尖峰 ECD 的总抗体之间存在中度到高度相关性:这项研究为了解 KT 在体液免疫方面的相对脆弱性和 SARS-CoV-2 不断演变的变异提供了重要的见解。这些发现有助于评估疫苗反应和推荐 KT 的疫苗接种期。
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引用次数: 0
Norepinephrine may promote the progression of Fusobacterium nucleatum related colorectal cancer via quorum sensing signalling. 去甲肾上腺素可通过法定人数感应信号促进与核酸镰刀菌相关的结直肠癌的进展。
IF 5.2 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-09 DOI: 10.1080/21505594.2024.2350904
Xinhao Du, Zhenzhen Tang, Li Yan, Ling Zhang, Qiao Zheng, Xianghao Zeng, Qing Hu, Qian Tian, Lanfan Liang, Xinyu Zhao, Jun Li, Ming Zhao, Xiangsheng Fu

Fusobacterium nucleatum (F. nucleatum) is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of F. nucleatum in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of F. nucleatum related CRC (p < 0.01). In vitro studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of F. nucleatum. Moreover, chronic stress significantly increased the colon tumour burden of ApcMin/+ mice infected with F. nucleatum (p < 0.01), which was decreased by a catecholamine inhibitor (p < 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of F. nucleatum related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.

核叉杆菌(F. nucleatum)与结直肠癌(CRC)的肿瘤发生密切相关。我们旨在研究宿主去甲肾上腺素对核分枝杆菌在 CRC 中致癌性的影响,并揭示其潜在机制。结果发现,去甲肾上腺素和细菌法定量传感(QS)分子自动诱导因子-2(AI-2)均与F. nucleatum相关CRC的进展呈正相关(p 在体外研究中,去甲肾上腺素诱导QS相关基因上调,促进F. nucleatum的毒力和增殖。此外,慢性应激通过细菌 QS 信号传导,明显增加了感染 F. nucleatum 的 ApcMin/+ 小鼠的结肠肿瘤负荷(p p F. nucleatum related CRC)。这些初步数据为通过靶向宿主激素-细菌 QS 部门间信号来管理病原菌提供了一种新策略。
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引用次数: 0
Helicobacter pylori East Asian type CagA hijacks more SHIP2 by its EPIYA-D motif to potentiate the oncogenicity. 幽门螺杆菌东亚型CagA通过其EPIYA-D基团劫持更多的SHIP2,从而增强致癌能力。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-09 DOI: 10.1080/21505594.2024.2375549
Xiaofei Ji, Qianwen Wu, Xinying Cao, Shuzhen Liu, Jianhui Zhang, Si Chen, Jiangfan Shan, Ying Zhang, Boqing Li, Huilin Zhao

CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.

CagA 是幽门螺杆菌注入宿主细胞的重要致癌因子,分为两个亚型:东亚型(CagAE)以 EPIYA-D 基因为特征,西方型(CagAW)以 EPIYA-C 基因为特征。据报道,CagAE 的致癌性高于 CagAW,但其根本原因尚不完全清楚。SHIP2 是一种细胞内磷酸酶,可被 CagA 招募,从而扰乱细胞内信号通路的平衡。在本研究中,我们发现SHIP2是CagAE致癌率更高的原因之一。共免疫沉淀和Pull-down实验表明,CagAE比CagAW结合更多的SHIP2。免疫荧光染色显示,CagAE 将更多的 SHIP2 募集到质膜上,催化 PI(3,4,5)P3 转化为 PI(3,4)P2。这种改变会导致 Akt 信号的更高活化,从而增强 IL-8 的分泌、迁移和感染细胞的入侵。SPR 分析表明,CagAE 与 SHIP2 之间更强的相互作用源于 CagAE 的 EPIYA-D 矩阵与 SHIP2 的 SH2 结构域之间更高的亲和力。结构分析表明,EPIYA-D 中位于 Y + 5 位置的 Phe 残基起着关键作用。将CagAE的Phe突变为Asp(EPIYA-C基序中的相应残基)或Ala后,下游Akt信号的激活作用减弱,感染细胞的恶性转化得到缓解。这些发现揭示了CagAE通过其EPIYA-D基序劫持SHIP2以增强其致癌性,从而更好地理解了幽门螺杆菌CagAE更高的致癌风险。
{"title":"<i>Helicobacter pylori</i> East Asian type CagA hijacks more SHIP2 by its EPIYA-D motif to potentiate the oncogenicity.","authors":"Xiaofei Ji, Qianwen Wu, Xinying Cao, Shuzhen Liu, Jianhui Zhang, Si Chen, Jiangfan Shan, Ying Zhang, Boqing Li, Huilin Zhao","doi":"10.1080/21505594.2024.2375549","DOIUrl":"10.1080/21505594.2024.2375549","url":null,"abstract":"<p><p>CagA is a significant oncogenic factor injected into host cells by <i>Helicobacter pylori</i>, which is divided into two subtypes: East Asian type (CagA<sup>E</sup>), characterized by the EPIYA-D motif, and western type (CagA<sup>W</sup>), harboring the EPIYA-C motif. CagA<sup>E</sup> has been reported to have higher carcinogenicity than CagA<sup>W</sup>, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagA<sup>E</sup>. Co-Immunoprecipitation and Pull-down assays showed that CagA<sup>E</sup> bind more SHIP2 than CagA<sup>W</sup>. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagA<sup>E</sup> to the plasma membrane catalyzes the conversion of PI(3,4,5)P<sub>3</sub> into PI(3,4)P<sub>2</sub>. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagA<sup>E</sup> and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagA<sup>E</sup> and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagA<sup>E</sup> into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagA<sup>E</sup> hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of <i>H. pylori</i> CagA<sup>E</sup>.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2375549"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Porcine reproductive and respiratory syndrome virus infects the reproductive system of male piglets and impairs development of the blood-testis barrier. 猪繁殖与呼吸综合征病毒感染雄性仔猪的生殖系统,并损害血液-睾丸屏障的发育。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-29 DOI: 10.1080/21505594.2024.2384564
Bingzhou Huang, Fengqin Li, Dong You, Lishuang Deng, Tong Xu, Siyuan Lai, Yanru Ai, Jianbo Huang, Yuancheng Zhou, Liangpeng Ge, Xiu Zeng, Zhiwen Xu, Ling Zhu

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood - testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and β-catenin were downregulated in cell - cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. H2O2, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.

猪繁殖与呼吸综合征病毒(PRRSV)是一种威胁全球养猪业的高传染性疾病。最近的研究主要关注 PRRSV 对公猪生殖系统的损害,但缺乏病理研究。因此,我们研究了感染 PRRSV 的公猪的致病机制。免疫组化分析证实,大体和组织病理学变化表明 PRRSV 影响了整个生殖系统。PRRSV 感染了肥大细胞和精原细胞。为了验证仔猪感染 PRRSV 会影响血液-睾丸屏障(BTB)发育的新假设,我们研究了 PRRSV 对 BTB 损伤的病理变化。PRRSV感染明显降低了构成BTB的Sertoli细胞的数量和增殖能力。细胞-细胞连接处的Zonula occludens-1和β-catenin下调。转录组分析表明,涉及睾丸中Leydig细胞、Sertoli细胞和紧密连接的生长和发育的几个关键基因和信号通路被下调。与凋亡、坏死、炎症和氧化应激相关的通路被激活,而与激素分泌相关的通路则受到抑制。许多 Sertoli 细胞和精原细胞在早期分化过程中发生凋亡。受感染的仔猪表现出雄激素分泌紊乱,导致睾酮和抗苗勒管激素水平显著降低。细胞因子风暴出现,肿瘤坏死因子-α和白细胞介素-6等细胞因子明显上调。氧化应激损伤标志物(即 H2O2、丙二醛和谷胱甘肽)上调,而抗氧化酶活性(即超氧化物歧化酶、总抗氧化能力和过氧化氢酶)下调。我们的研究结果表明,PRRSV 感染了雄性生殖系统的多个器官,从而影响了 BTB 的生长。
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引用次数: 0
Oral inoculation of Fusobacterium nucleatum exacerbates ulcerative colitis via the secretion of virulence adhesin FadA. 通过分泌毒力粘附素 FadA,口服接种核酸镰刀菌会加重溃疡性结肠炎。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-09 DOI: 10.1080/21505594.2024.2399217
Donghao Li, Zongwei Li, Lei Wang, Yan Zhang, Shoubin Ning

Fusobacterium nucleatum (F. nucleatum), an anaerobic resident of the oral cavity, is increasingly recognized as a contributing factor to ulcerative colitis (UC). The adhesive properties of F. nucleatum are mediated by its key virulence protein, FadA adhesin. However, further investigations are needed to understand the pathogenic mechanisms of this oral pathogen in UC. The present study aimed to explore the role of the FadA adhesin in the colonization and invasion of oral F. nucleatum in dextran sulphate sodium (DSS)-induced colitis mice via molecular techniques. In this study, we found that oral inoculation of F. nucleatum strain carrying the FadA adhesin further exacerbated DSS-induced colitis, leading to elevated alveolar bone loss, disease severity, and mortality. Additionally, CDH1 gene knockout mice treated with DSS presented increases in body weight and alveolar bone density, as well as a reduction in disease severity. Furthermore, FadA adhesin adhered to its mucosal receptor E-cadherin, leading to the phosphorylation of β-catenin and the degradation of IκBα, the activation of the NF-κB signalling pathway and the upregulation of downstream cytokines. In conclusion, this research revealed that oral inoculation with F. nucleatum facilitates experimental colitis via the secretion of the virulence adhesin FadA. Targeting the oral pathogen F. nucleatum and its virulence factor FadA may represent a promising therapeutic approach for a portion of UC patients.

核滑杆菌(Fusobacterium nucleatum,F. nucleatum)是口腔中的一种厌氧居民,越来越被认为是溃疡性结肠炎(UC)的致病因素。核酸杆菌的粘附特性是由其关键毒力蛋白 FadA 粘合素介导的。然而,要了解这种口腔病原体在溃疡性结肠炎中的致病机制还需要进一步研究。本研究旨在通过分子技术探讨 FadA 粘附蛋白在葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠口腔核酸桿菌定植和入侵中的作用。在这项研究中,我们发现口腔接种携带 FadA 黏附因子的 F. nucleatum 菌株会进一步加剧右旋糖酐硫酸钠(DSS)诱导的结肠炎,导致牙槽骨损失、疾病严重程度和死亡率升高。此外,CDH1 基因敲除小鼠经 DSS 治疗后,体重和牙槽骨密度增加,疾病严重程度降低。此外,FadA粘附蛋白与其粘膜受体E-cadherin粘附,导致β-catenin磷酸化、IκBα降解、NF-κB信号通路激活和下游细胞因子上调。总之,这项研究揭示了口腔接种F. nucleatum可通过分泌毒力粘附素FadA促进实验性结肠炎的发生。针对口腔病原体F. nucleatum及其毒力因子FadA可能是治疗部分UC患者的一种很有前景的方法。
{"title":"Oral inoculation of <i>Fusobacterium nucleatum</i> exacerbates ulcerative colitis via the secretion of virulence adhesin FadA.","authors":"Donghao Li, Zongwei Li, Lei Wang, Yan Zhang, Shoubin Ning","doi":"10.1080/21505594.2024.2399217","DOIUrl":"10.1080/21505594.2024.2399217","url":null,"abstract":"<p><p><i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>), an anaerobic resident of the oral cavity, is increasingly recognized as a contributing factor to ulcerative colitis (UC). The adhesive properties of <i>F. nucleatum</i> are mediated by its key virulence protein, FadA adhesin. However, further investigations are needed to understand the pathogenic mechanisms of this oral pathogen in UC. The present study aimed to explore the role of the FadA adhesin in the colonization and invasion of oral <i>F. nucleatum</i> in dextran sulphate sodium (DSS)-induced colitis mice via molecular techniques. In this study, we found that oral inoculation of <i>F. nucleatum</i> strain carrying the FadA adhesin further exacerbated DSS-induced colitis, leading to elevated alveolar bone loss, disease severity, and mortality. Additionally, CDH1 gene knockout mice treated with DSS presented increases in body weight and alveolar bone density, as well as a reduction in disease severity. Furthermore, FadA adhesin adhered to its mucosal receptor E-cadherin, leading to the phosphorylation of β-catenin and the degradation of IκBα, the activation of the NF-κB signalling pathway and the upregulation of downstream cytokines. In conclusion, this research revealed that oral inoculation with <i>F. nucleatum</i> facilitates experimental colitis via the secretion of the virulence adhesin FadA. Targeting the oral pathogen <i>F. nucleatum</i> and its virulence factor FadA may represent a promising therapeutic approach for a portion of UC patients.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2399217"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The formidable guardian: Type 3 immunity in the intestine of pigs. 强大的守护者猪肠道中的 3 型免疫。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-08 DOI: 10.1080/21505594.2024.2424325
Zhipeng Yang, Dou Zhang, Zhoudan Jiang, Jian Peng, Hongkui Wei

Well-intestinal health is crucial for better growth performance in pigs. Type 3 immunity, which is one of the three types of immune responses in mammals, plays a vital role in maintaining intestinal homoeostasis. Therefore, we initially introduce the type 3 immune cells in the intestine of pigs, including their distribution, development, and function. We then discuss the type 3 immune response under infection, encompassing bacterial, fungal, and viral infections. It also covers two major stresses in pigs: heat stress and weaning stress. Lastly, we discuss the effects of various nutrients and feed additives on the regulation of the type 3 immune response in pigs under infection. This review aims to contribute to the understanding of the interaction between infection and type 3 immunity in pigs and to illustrate how various nutrients modulate the type 3 immune response in pigs under diverse infections.

良好的肠道健康对提高猪的生长性能至关重要。3 型免疫是哺乳动物三种免疫反应之一,在维持肠道平衡方面发挥着重要作用。因此,我们首先介绍猪肠道中的 3 型免疫细胞,包括其分布、发育和功能。然后,我们将讨论感染情况下的 3 型免疫反应,包括细菌、真菌和病毒感染。本章还涉及猪的两大应激:热应激和断奶应激。最后,我们还讨论了各种营养物质和饲料添加剂对猪在感染情况下的 3 型免疫反应的调节作用。本综述旨在帮助人们了解猪感染与 3 型免疫之间的相互作用,并说明各种营养物质如何调节猪在不同感染情况下的 3 型免疫反应。
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引用次数: 0
Loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing K1-ST23 hypervirulent Klebsiella pneumoniae. 一种不产碳青霉烯酶的 K1-ST23 型高病毒性肺炎克雷伯菌对头孢他啶-阿维菌素敏感性的丧失和增益。
IF 5.2 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-02 DOI: 10.1080/21505594.2024.2348251
Jiankang Zhao, Danni Pu, Ziyao Li, Yulin Zhang, Xinmeng Liu, Xianxia Zhuo, Binghuai Lu, Bin Cao

Objectives: This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent Klebsiella pneumoniae (hvKp).

Methods: Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted.

Results: Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes blaCTX-M-15 and blaCTX-M-71, respectively, but KP30086 lost both. Cloning of gene blaCTX-M-71 and conjugation experiment of blaCTX-M-71-carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105.

Conclusions: In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying blaCTX-M-71 and mutated OmpK36 had a synergetic effect on the resistance.

研究目的本研究旨在揭示非碳青霉烯酶生产型高病毒性肺炎克雷伯菌(hvKp)对头孢他啶-阿维巴坦易感性丧失和增益的内在机制。方法:我们从一名老年男性患者身上纵向采集了3株非碳青霉烯酶生产型K1-ST23 hvKp菌株(KP29105、KP29499和KP30086),间隔时间为一个月。研究人员对这些菌株进行了抗菌药敏感性检测、全基因组测序、转录组测序、基因克隆、质粒连接、实时定量 PCR(qRT-PCR)和 SDS-PAGE(十二烷基硫酸钠-聚丙烯酰胺凝胶电泳):结果:在3株hvKp菌株中,KP29105对第三代和第四代头孢菌素耐药,KP29499对头孢唑肟-阿维巴坦和碳青霉烯类耐药,而KP30086恢复了对头孢唑肟-阿维巴坦、亚胺培南和美罗培南的敏感性,但对厄他培南保持低水平耐药。KP29105 和 KP29499 分别携带质粒编码基因 blaCTX-M-15 和 blaCTX-M-71,但 KP30086 却失去了这两种基因。基因 blaCTX-M-71 的克隆和携带 blaCTX-M-71 的质粒的共轭实验表明,转化株和转接株对头孢他啶-阿维巴坦敏感,但 MICs 增加了 8 倍多。添加外膜渗透剂可使头孢他啶-阿维菌素的 MIC 降低 32 倍,表明孔蛋白在头孢他啶-阿维菌素耐药性中起着关键作用。这 3 个分离株的 OmpK35 没有表达,KP29499 和 KP30086 的 OmpK36 有一个新的氨基酸取代(L359R)。SDS-PAGE和qRT-PCR显示,与KP29105相比,KP29499和KP30086的孔蛋白OmpK36表达明显下调:综上所述,我们报道了非碳青霉烯酶产hvKp菌株对头孢他啶-阿维菌素的罕见耐药性。携带 blaCTX-M-71 和突变 OmpK36 的耐药质粒对耐药性有协同作用。
{"title":"Loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing K1-ST23 hypervirulent <i>Klebsiella pneumoniae</i>.","authors":"Jiankang Zhao, Danni Pu, Ziyao Li, Yulin Zhang, Xinmeng Liu, Xianxia Zhuo, Binghuai Lu, Bin Cao","doi":"10.1080/21505594.2024.2348251","DOIUrl":"10.1080/21505594.2024.2348251","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent <i>Klebsiella pneumoniae</i> (hvKp).</p><p><strong>Methods: </strong>Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted.</p><p><strong>Results: </strong>Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes <i>bla</i><sub>CTX-M-15</sub> and <i>bla</i><sub>CTX-M-71</sub>, respectively, but KP30086 lost both. Cloning of gene <i>bla</i><sub>CTX-M-71</sub> and conjugation experiment of <i>bla</i><sub>CTX-M-71</sub>-carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105.</p><p><strong>Conclusions: </strong>In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying <i>bla</i><sub>CTX-M-71</sub> and mutated OmpK36 had a synergetic effect on the resistance.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2348251"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11067985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality. 苍白螺旋体上的血小板源性主要组织相容性复合体 I 类涂层可减轻自然杀伤细胞的致死率。
IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-14 DOI: 10.1080/21505594.2024.2350892
Qiu-Yan Xu, Xin-Qi Zheng, Wei-Ming Ye, Dong-Yu Yi, Ze Li, Qing-Qi Meng, Man-Li Tong, Dan Liu, Tian-Ci Yang

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

苍白盘尾丝菌的躲避策略给抗击和根除梅毒带来了重大挑战。为了弄清苍白螺旋体逃避NK介导的免疫监视的机制,研究人员进行了实验来探索苍白螺旋体、NK细胞和血小板之间的交叉对话关系。苍白球粘附、激活并促进血小板分泌微粒。与苍白球预孵育后,血小板表达并分泌高水平的 MHC I 类,随后将其转移到苍白球表面,可能诱导出一种以苍白球表面 MHC I 类 "伪表达"(以下简称 MHC I 类 "伪表达")为特征的免疫表型。polA mRNA 检测显示,血小板预培养 T. pallidum 组的 polA 转录本拷贝数明显高于 T. pallidum 组。T. pallidum的存活率与polA mRNA的存活率一致,这表明T. pallidum与血小板预孵育可减轻NK细胞的致死率。血小板在苍白球表面伪表达了MHC I类配体,促进了与NK细胞上具有两个免疫球蛋白结构域和长胞质尾3(KIR2DL3)的杀伤细胞免疫球蛋白样受体的结合,并启动了Vav1的去磷酸化和Crk的磷酸化,最终降低了NK细胞的致死率。我们的发现阐明了血小板将 MHC I 类转移到苍白球表面以逃避 NK 细胞免疫清除的机制。
{"title":"Platelet-derived major histocompatibility complex class I coating on <i>Treponema pallidum</i> attenuates natural killer cell lethality.","authors":"Qiu-Yan Xu, Xin-Qi Zheng, Wei-Ming Ye, Dong-Yu Yi, Ze Li, Qing-Qi Meng, Man-Li Tong, Dan Liu, Tian-Ci Yang","doi":"10.1080/21505594.2024.2350892","DOIUrl":"10.1080/21505594.2024.2350892","url":null,"abstract":"<p><p>The evasive tactics of <i>Treponema pallidum</i> pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify <i>T. pallidum's</i> mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among <i>T. pallidum</i>, NK cells, and platelets. <i>T. pallidum</i> adhered to, activated, and promoted particle secretion of platelets. After preincubation with <i>T. pallidum</i>, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of <i>T. pallidum</i>, potentially inducing an immune phenotype characterized by the \"pseudo-expression\" of MHC class I on the surface of <i>T. pallidum</i> (hereafter referred to a \"pseudo-expression\" of MHC class I). The <i>polA</i> mRNA assay showed that platelet-preincubated <i>T. pallidum</i> group exhibited a significantly higher copy number of <i>polA</i> transcript than the <i>T. pallidum</i> group. The survival rate of <i>T. pallidum</i> mirrored that of <i>polA</i> mRNA, indicating that preincubation of <i>T. pallidum</i> with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the <i>T. pallidum</i> surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the <i>T. pallidum</i> surface to evade NK cell immune clearance.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2350892"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","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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Virulence
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