Salmonella typhimurium

鼠伤寒沙门氏菌
  • 文章类型: Journal Article
    本研究旨在评价耐断奶断奶仔猪抗鼠伤寒沙门氏菌感染的效果。研究重点是LA对肠道菌群组成的影响,增长业绩,和沙门氏菌粪便脱落。结果表明,补充LA显着改善了平均日增重,并降低了腹泻的患病率和严重程度。粪便分析显示,补充LA的组沙门氏菌脱落减少。此外,LA显著改变了肠道微生物群的组成,增加有益芽孢杆菌的水平,减少有害的变形杆菌和螺旋藻的水平。组织病理学检查显示,与对照组相比,LA处理的仔猪的肠道损伤较小。该研究还观察到LA影响与碳水化合物相关的代谢功能,氨基酸,和脂肪酸代谢,从而增强肠道健康和抵御感染的能力。LA组粪便中短链脂肪酸浓度较高,表明改善了肠道微生物活性。补充LA丰富了有益细菌的数量,包括链球菌,梭菌属,和双歧杆菌,同时减少有害细菌的数量,如大肠杆菌和弯曲杆菌。这些发现表明LA作为猪营养的益生菌替代品的潜力,为肠道微生物群提供针对沙门氏菌感染的保护作用。
    This study aimed to evaluate the efficacy of Lactiplantibacillus argentoratensis AGMB00912 (LA) in reducing Salmonella Typhimurium infection in weaned piglets. The investigation focused on the influence of LA on the gut microbiota composition, growth performance, and Salmonella fecal shedding. The results indicated that LA supplementation significantly improved average daily gain and reduced the prevalence and severity of diarrhea. Fecal analysis revealed reduced Salmonella shedding in the LA-supplemented group. Furthermore, LA notably altered the composition of the gut microbiota, increasing the levels of beneficial Bacillus and decreasing those of harmful Proteobacteria and Spirochaetes. Histopathological examination showed less intestinal damage in LA-treated piglets than in the controls. The study also observed that LA affected metabolic functions related to carbohydrate, amino acid, and fatty acid metabolism, thereby enhancing gut health and resilience against infection. Short-chain fatty acid concentrations in the feces were higher in the LA group, suggesting improved gut microbial activity. LA supplementation enriched the population of beneficial bacteria, including Streptococcus, Clostridium, and Bifidobacterium, while reducing the number of harmful bacteria, such as Escherichia and Campylobacter. These findings indicate the potential of LA as a probiotic alternative for swine nutrition, offering protective effects to the gut microbiota against Salmonella infection.
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  • 文章类型: Journal Article
    木糖与苯丙氨酸和木糖与脯氨酸的美拉德反应产物(MRP)具有较高的抗菌活性。然而,MRP中的活性抗菌化合物尚未被鉴定或分离。本研究旨在分离两种抗菌MRPs中的活性化合物。使用硅胶色谱法和高效液相色谱法分离和纯化MRP溶液的有机层。分离的化合物的化学结构通过质谱和核磁共振波谱测定。这些化合物在25°C下以0.25mM的浓度抑制蜡状芽孢杆菌和鼠伤寒沙门氏菌的生长7天。此外,分离的化合物在25°C下以0.5-1.0mM的浓度抑制了生菜和鸡大腿的天然微生物群的生长2天。在MRP中发现的抗菌化合物表现出广泛的有效性,并表明它们作为替代防腐剂的潜力。
    Maillard reaction products (MRPs) of xylose with phenylalanine and xylose with proline exhibit high antibacterial activity. However, the active antibacterial compounds in MRPs have not yet been identified or isolated. This study aimed to isolate the active compounds in the two antibacterial MRPs. The organic layer of the MRP solution was separated and purified using silica gel chromatography and high-performance liquid chromatography. The chemical structures of the isolated compounds were determined by mass spectrometry and nuclear magnetic resonance spectroscopy. The compounds inhibited the growth of Bacillus cereus and Salmonella Typhimurium at 25 °C for 7 days at a concentration of 0.25 mM. Furthermore, the isolated compounds inhibited the growth of naturally occurring microflora of lettuce and chicken thighs at 25 °C for 2 days at a concentration of 0.5-1.0 mM. The antibacterial compounds found in MRPs demonstrated a wide range of effectiveness and indicated their potential as alternative preservatives.
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    文章类型: Journal Article
    我们报告了一个25岁女孩的严重病例,她抱怨虚弱,腹泻,呕吐,感染性疾病和临床免疫学研究中心的腹部疼痛和低血压。从2月25日至2月29日的历史,她在印度,3月1日,这个问题始于水样腹泻,然后是呕吐。她用蘑菇吃披萨,之后病情恶化。粪便培养显示非伤寒沙门氏菌(非甲状腺沙门氏菌),这是胃肠炎的主要原因,菌血症和影响其他几个身体系统。由于ARDS(急性呼吸窘迫综合征)的发展,她的病情恶化,为此她正在进行机械通气。进行了Vitec机,鉴定出伤寒沙门氏菌.我们的目标是通过早期诊断来管理和治疗该患者。她服用了头孢曲松,静脉输液和对症治疗,但由于耐药性美罗培南开始治疗,患者的病情得到改善。从血清学来看,没有证据表明存在免疫功能低下的状态,因此,作为具有免疫能力的患者的重症病例,该病例反映了及时诊断和管理以及人群食品安全实践的重要性。随访时,她病情稳定,3周后出院。未来的研究需要继续进行有关新菌株的研究,有效的治疗策略和诊断,以防止发病率和死亡率。
    We report a severe case of a 25-year-old girl presented with complaints of weakness, diarrhoea, vomiting, pain in abdomen and hypotension at Infectious Diseases and Clinical Immunology Research Center. From history on 25 February till 29 February she was in India and on 1 march this problem started with watery diarrhoea followed by vomiting. She ate pizza with mushroom following which her condition worsened. Stool culture revealed salmonella nontyphi (nonthyphodal Salmonella)and this is leading cause for gastroenteritis, bacteremia and affects several other bodily system. Her condition deteriorated due to the development of ARDS (acute respiratory distress syndrome) and for this she was on mechanical ventilation. Vitec machine was performed, which identified Salmonella typhi murium. Our goal is to manage and treat this patient well by early diagnosis. She was given ceftriaxone, iv fluids and symptomatic treatment but due to resistance meropenem was started and the patient\'s condition improved. From serology there was no evidence of immunocompromised state so being a severe case of immunocompetent patient this case reflects the importance of timely diagnosis and management together with food safety practices in population. On follow up she was stable and discharged after 3 weeks. Future research studies need to be continued regarding newer strains, effective treatment strategies and diagnostics to prevent morbidity and mortality.
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  • 文章类型: Journal Article
    食源性沙门氏菌病的发病率不断上升,对食品安全和公共卫生构成了重大的全球威胁。随着沙门氏菌的抗生素耐药性持续上升,人们对噬菌体作为潜在替代品的兴趣日益浓厚。在这项研究中,我们与世隔绝,characterized,并评价了裂解噬菌体L223在鸡肉中的生防效果。噬菌体L223在广泛的温度(20-70°C)和pH水平(2-11)范围内表现出强大的稳定性,并表现出靶向沙门氏菌的有限宿主范围。,尤其是鼠伤寒沙门氏菌和肠炎沙门氏菌。L223的表征显示30分钟的短潜伏期和515PFU/细胞的大量爆发。基因组分析将L223分类为Caudoviricetes类,Guernseyvirinae亚科和Jerseyvirus属,dsDNA基因组大小为44,321bp,GC含量为47.9%,具有72个缺乏抗菌素耐药性的编码序列,毒力因子,毒素,和tRNA基因。在孵育2、4和6小时后,应用L223显着(p<0.005)减少了鼠伤寒沙门氏菌ATCC14,028计数1.24、2.17和1.55logCFU/片,分别,在实验污染的鸡胸肉样本中。这些发现凸显了沙门氏菌噬菌体L223作为减轻食品中沙门氏菌污染的有前途的生物防治剂的潜力。强调其与加强食品安全协议的相关性。
    The escalating incidence of foodborne salmonellosis poses a significant global threat to food safety and public health. As antibiotic resistance in Salmonella continues to rise, there is growing interest in bacteriophages as potential alternatives. In this study, we isolated, characterized, and evaluated the biocontrol efficacy of lytic phage L223 in chicken meat. Phage L223 demonstrated robust stability across a broad range of temperatures (20-70 °C) and pH levels (2-11) and exhibited a restricted host range targeting Salmonella spp., notably Salmonella Typhimurium and Salmonella Enteritidis. Characterization of L223 revealed a short latent period of 30 min and a substantial burst size of 515 PFU/cell. Genomic analysis classified L223 within the Caudoviricetes class, Guernseyvirinae subfamily and Jerseyvirus genus, with a dsDNA genome size of 44,321 bp and 47.9% GC content, featuring 72 coding sequences devoid of antimicrobial resistance, virulence factors, toxins, and tRNA genes. Application of L223 significantly (p < 0.005) reduced Salmonella Typhimurium ATCC 14,028 counts by 1.24, 2.17, and 1.55 log CFU/piece after 2, 4, and 6 h of incubation, respectively, in experimentally contaminated chicken breast samples. These findings highlight the potential of Salmonella phage L223 as a promising biocontrol agent for mitigating Salmonella contamination in food products, emphasizing its relevance for enhancing food safety protocols.
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  • 文章类型: Journal Article
    为了生存和复制,沙门氏菌已经进化了进入隐窝肠上皮细胞的机制。然而,鼠伤寒沙门氏菌对干细胞和祖细胞的影响,它们负责肠上皮自我更新和保护的能力,尚不清楚。鉴于肠道类器官的生长是由干细胞和祖细胞活动维持的,我们使用这个模型来记录鼠伤寒沙门氏菌感染对上皮增殖和分化的影响,并将其与小鼠体内沙门氏菌感染模型进行了比较。在肠段中,盲肠优先被沙门氏菌作为目标。受感染的隐窝和类器官的分析显示长度和大小增加,分别。感染的隐窝和类器官的mRNA转录谱指出上调的EGFR依赖性信号,与分泌细胞谱系分化减少有关。最后,我们表明,类器官适合模拟沙门氏菌对干细胞和祖细胞的影响,具有极大的潜力,可以大大减少在该主题的科学研究中使用动物。在这两种模型中,EGFR通路,对干细胞和祖细胞的增殖和分化至关重要,沙门氏菌失调,提示反复感染可能对隐窝完整性和进一步的肿瘤发生产生影响。
    In order to survive and replicate, Salmonella has evolved mechanisms to gain access to intestinal epithelial cells of the crypt. However, the impact of Salmonella Typhimurium on stem cells and progenitors, which are responsible for the ability of the intestinal epithelium to renew and protect itself, remains unclear. Given that intestinal organoids growth is sustained by stem cells and progenitors activity, we have used this model to document the effects of Salmonella Typhimurium infection on epithelial proliferation and differentiation, and compared it to an in vivo model of Salmonella infection in mice. Among gut segments, the caecum was preferentially targeted by Salmonella. Analysis of infected crypts and organoids demonstrated increased length and size, respectively. mRNA transcription profiles of infected crypts and organoids pointed to upregulated EGFR-dependent signals, associated with a decrease in secretory cell lineage differentiation. To conclude, we show that organoids are suited to mimic the impact of Salmonella on stem cells and progenitors cells, carrying a great potential to drastically reduce the use of animals for scientific studies on that topic. In both models, the EGFR pathway, crucial to stem cells and progenitors proliferation and differentiation, is dysregulated by Salmonella, suggesting that repeated infections might have consequences on crypt integrity and further oncogenesis.
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  • 文章类型: Journal Article
    幽门螺杆菌引起全球流行的感染,与慢性胃炎甚至胃癌的发展高度相关。随着抗生素耐药性的增加,科学家们已经开始寻找更好的疫苗设计策略来根除幽门螺杆菌定植。然而,虽然目前的策略更喜欢用单一的幽门螺杆菌抗原配制疫苗,他们的潜力尚未充分发挥。外膜囊泡(OMV)是潜在的平台,因为它们可以递送多种抗原。在这项研究中,我们设计了三种关键的幽门螺杆菌抗原蛋白(UreB,卡加,和VacA)到源自鼠伤寒沙门氏菌的OMV表面(S.使用血红蛋白蛋白酶(Hbp)自转运蛋白系统的鼠伤寒)突变菌株。在各种淘汰赛策略中,我们发现,从ΔrfbPΔfliCΔfljBΔompA突变体中分离出的OMV可以引起免疫球蛋白G(IgG)和A(IgA)水平的明显增加,并有效地触发T辅助细胞1-和17-偏向的细胞免疫反应,在预防幽门螺杆菌方面发挥着至关重要的作用。接下来,衍生自ΔrfbPΔfliCΔfljBΔompA突变体的OMV用作载体以递送幽门螺杆菌抗原的不同组合。小鼠模型中的抗体和细胞因子水平以及攻击实验表明,共同递送UreB和CagA可以保护免受幽门螺杆菌和抗原特异性T细胞应答。总之,从鼠伤寒沙门氏菌ΔrfbPΔfliCΔfljBΔompA突变株作为载体,同时使用Hbp自转运蛋白系统导入幽门螺杆菌UreB和CagA作为抗原蛋白,将大大有利于控制幽门螺杆菌感染。
    外膜囊泡(OMV),作为一种新型的抗原递送平台,已用于各种病原体甚至肿瘤的疫苗设计。肠病沙门氏菌(S.鼠伤寒),作为一种易于工程化并具有佐剂功效和免疫刺激能力的细菌,已成为继大肠杆菌之后纯化OMV的首选细菌载体。本研究的重点是幽门螺杆菌的设计;(H.幽门螺杆菌)疫苗,利用基因修饰的沙门氏菌OMV呈递幽门螺杆菌的几种主要抗原,包括UreB,VacA和CagA.筛选并鉴定了最佳的沙门氏菌OMV递送载体和抗原组合,为H.pylori疫苗的开发提供了新的思路,并为其他难以开发的细菌疫苗提供了一个集成的抗原递送平台,病毒,甚至肿瘤。
    Helicobacter pylori causes globally prevalent infections that are highly related to chronic gastritis and even development of gastric carcinomas. With the increase of antibiotic resistance, scientists have begun to search for better vaccine design strategies to eradicate H. pylori colonization. However, while current strategies prefer to formulate vaccines with a single H. pylori antigen, their potential has not yet been fully realized. Outer membrane vesicles (OMVs) are a potential platform since they could deliver multiple antigens. In this study, we engineered three crucial H. pylori antigen proteins (UreB, CagA, and VacA) onto the surface of OMVs derived from Salmonella enterica serovar Typhimurium (S. Typhimurium) mutant strains using the hemoglobin protease (Hbp) autotransporter system. In various knockout strategies, we found that OMVs isolated from the ΔrfbP ΔfliC ΔfljB ΔompA mutants could cause distinct increases in immunoglobulin G (IgG) and A (IgA) levels and effectively trigger T helper 1- and 17-biased cellular immune responses, which perform a vital role in protecting against H. pylori. Next, OMVs derived from ΔrfbP ΔfliC ΔfljB ΔompA mutants were used as a vector to deliver different combinations of H. pylori antigens. The antibody and cytokine levels and challenge experiments in mice model indicated that co-delivering UreB and CagA could protect against H. pylori and antigen-specific T cell responses. In summary, OMVs derived from the S. Typhimurium ΔrfbP ΔfliC ΔfljB ΔompA mutant strain as the vector while importing H. pylori UreB and CagA as antigenic proteins using the Hbp autotransporter system would greatly benefit controlling H. pylori infection.
    Outer membrane vesicles (OMVs), as a novel antigen delivery platform, has been used in vaccine design for various pathogens and even tumors. Salmonella enterica serovar Typhimurium (S. Typhimurium), as a bacterium that is easy to engineer and has both adjuvant efficacy and immune stimulation capacity, has become the preferred bacterial vector for purifying OMVs after Escherichia coli. This study focuses on the design of Helicobacter pylori ;(H. pylori) vaccines, utilizing genetically modified Salmonella OMVs to present several major antigens of H. pylori, including UreB, VacA and CagA. The optimal Salmonella OMV delivery vector and antigen combinations are screened and identified, providing new ideas for the development of H. pylori vaccines and an integrated antigen delivery platform for other difficult to develop vaccines for bacteria, viruses, and even tumors.
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  • 文章类型: Journal Article
    肠道微生物群是在肠道健康和疾病状况中起关键作用的微生物。考虑到肠道微生物群的特征功能,在这项研究中,罗伊氏乳杆菌TPC32(L.罗伊特TPC32)被分离和鉴定,并通过IlluminaMiSeq测序平台分析其全基因组。结果表明,罗伊乳杆菌TPC32对酸和胆汁盐具有较高的抗性,具有良好的体外抗菌能力。因此,罗伊氏乳杆菌TPC32的基因组序列的总长度为2,214,495个碱基对,鸟嘌呤-胞嘧啶含量为38.81%。基于代谢注释,在2,212个蛋白质编码基因中,118和101注解碳水化合物代谢和辅因子和维生素的代谢,分别。同样,使用综合抗生素研究数据库(CARD)和毒力因子数据库(VFDB)注释耐药性和毒力基因,其中vatE和tetW耐药基因在罗伊氏乳杆菌TPC32中被注释,而毒力基因未被注释。罗伊氏乳杆菌TPC32的早期预防减少了鼠伤寒沙门氏菌(S.鼠伤寒)在小鼠中的感染。结果表明,罗伊乳杆菌TPC32能提高血清IgM,减少肠道细胞因子分泌,缓解肠道细胞因子风暴,通过提高sIgA表达来增强肠道生化屏障功能,加强肠道物理屏障功能。同时,基于16SrRNA分析,罗伊氏乳杆菌TPC32结果影响肠道微生物群从疾病状态的恢复并促进有益细菌的繁殖。这些结果为罗伊氏乳杆菌TPC32治疗肠道炎症的生物学功能和治疗潜力提供了新的见解。
    Gut microbiota are the microbial organisms that play a pivotal role in intestinal health and during disease conditions. Keeping in view the characteristic functions of gut microbiota, in this study, Lactobacillus reuteri TPC32 (L. reuteri TPC32) was isolated and identified, and its whole genome was analyzed by the Illumina MiSeq sequencing platform. The results revealed that L. reuteri TPC32 had high resistance against acid and bile salts with fine in vitro antibacterial ability. Accordingly, a genome sequence of L. reuteri TPC32 has a total length of 2,214,495 base pairs with a guanine-cytosine content of 38.81%. Based on metabolic annotation, out of 2,212 protein-encoding genes, 118 and 101 were annotated to carbohydrate metabolism and metabolism of cofactors and vitamins, respectively. Similarly, drug-resistance and virulence genes were annotated using the comprehensive antibiotic research database (CARD) and the virulence factor database (VFDB), in which vatE and tetW drug-resistance genes were annotated in L. reuteri TPC32, while virulence genes are not annotated. The early prevention of L. reuteri TPC32 reduced the Salmonella typhimurium (S. Typhimurium) infection in mice. The results show that L. reuteri TPC32 could improve the serum IgM, decrease the intestinal cytokine secretion to relieve intestinal cytokine storm, reinforce the intestinal biochemical barrier function by elevating the sIgA expression, and strengthen the intestinal physical barrier function. Simultaneously, based on the 16S rRNA analysis, the L. reuteri TPC32 results affect the recovery of intestinal microbiota from disease conditions and promote the multiplication of beneficial bacteria. These results provide new insights into the biological functions and therapeutic potential of L. reuteri TPC32 for treating intestinal inflammation.
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  • 文章类型: Journal Article
    水培耕作系统在营养丰富的食品的可持续生产中发挥着越来越重要的作用。水培新鲜农产品生产中的表面污染对作物的食品安全构成了风险,可能危害公众健康并造成行业经济损失。虽然消毒剂广泛用于商业水培农场,它们对表面人类病原体的有效性及其对植物健康和质量的影响尚不清楚。在这项研究中,我们评估了化学消毒剂在商业水培营养膜技术(NFT)系统中从无生命表面消除鼠伤寒沙门氏菌的功效。Further,我们评估了消毒剂对产量的影响,质量,生菜和罗勒的营养价值。Sanitizers(Virkon,LanXess,匹兹堡PA,美国;SaniDate12.0,生物安全系统,东哈特福德,CT,美国;KleenGrow,佩斯化学有限公司Delta,BC,加拿大;绿盾,UnitedLabsInc.,圣查尔斯,IL,美国;泽罗托尔,生物安全系统,东哈特福德,CT,美国;漂白,纯亮,ON,加拿大)针对接种在NFT表面上的鼠伤寒沙门氏菌进行了测试(营养库,不断增长的渠道,顶盖,排水管)。然后在商业NFT单元中进行的分裂小区实验中测试有效处理对生菜和罗勒的影响。作物产量,颜色,在整个作物生命周期中测量养分含量(叶绿素和类胡萝卜素)。虽然所有季铵化合物(QAC),SaniDate12.0(200ppm),Zorotol(5%),Virkon(1%)从商业NFT表面消除了鼠伤寒沙门氏菌,氯基消毒剂处理与大多数表面的水处理在统计学上相似。所有化学消毒剂都会影响产量,颜色,生菜和罗勒的营养价值。SaniDate12.0(200ppm)对农作物的危害最小,被确定为在商业水培环境中进一步验证的潜在候选者。这项研究的结果将转化为对行业的建议,并将有助于制定未来的食品安全准则和政策。
    Hydroponic farming systems play an increasingly important role in the sustainable production of nutrient-rich foods. The contamination of surfaces in hydroponic fresh produce production poses risks to the food safety of crops, potentially endangering public health and causing economic losses in the industry. While sanitizers are widely used in commercial hydroponic farms, their effectiveness against human pathogens on surfaces and their impact on plant health and quality are not known. In this study, we evaluated the efficacy of chemical sanitizers in eliminating Salmonella Typhimurium from inanimate surfaces in commercial hydroponic Nutrient Film Technique (NFT) systems. Further, we assessed the impact of sanitizers on the yield, quality, and nutritional value of lettuce and basil. Sanitizers (Virkon, LanXess, Pittsburgh, PA, USA; SaniDate 12.0, BioSafe Systems, East Hartford, CT, USA; KleenGrow, Pace Chemical Ltd., Delta, BC, Canada; Green Shield, United Labs Inc., St Charles, IL, USA; Zerotol, BioSafe Systems, East Hartford, CT, USA; Bleach, Pure Bright, ON, Canada) were tested against Salmonella Typhimurium inoculated on NFT surfaces (nutrient reservoir, growing channels, top covers, drain lines). The effective treatments were then tested for their impact on lettuce and basil in a split-plot experiment conducted in commercial NFT units. Crop yield, color, and nutrient content (chlorophyll and carotenoids) were measured throughout the crop life cycle. While all quaternary ammonium compounds (QAC), SaniDate 12.0 (200 ppm), Zorotol (5%), and Virkon (1%) eliminated Salmonella Typhimurium from commercial NFT surfaces, chlorine-based sanitizer treatments were statistically similar to water treatments on most surfaces. All chemical sanitizers impacted the yield, color, and nutritional value of lettuce and basil. SaniDate 12.0 (200 ppm) was the least detrimental to crops and was identified as a potential candidate for further validation in commercial hydroponic settings. The findings of this study will be translated into recommendations for the industry and will contribute to the development of future food safety guidelines and policies.
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  • 文章类型: Journal Article
    这里,我们证明了人类中性粒细胞与鼠伤寒沙门氏菌的相互作用促进了化学引诱物fMLP诱导的白三烯B4的合成。在这项工作中,我们发现细胞外ATP(eATP),其数量在组织损伤期间急剧增加,能有效调节fMLP诱导的白三烯B4的合成。影响的载体在很大程度上取决于细菌对嗜中性粒细胞的顺序刺激的特定阶段以及fMLP嘌呤能信号传导发生的阶段。5-脂氧合酶(5-LOX)的激活,白三烯生物合成的关键酶,取决于Ca2+的胞浆浓度的增加。我们证明在fMLP之前进行eATP处理,通过显著降低fMLP诱导的Ca2+瞬时跳跃的幅度,抑制白三烯合成。同时,当与FMLP一起添加或在FMLP之后不久添加时,eATP有效增强花生四烯酸代谢,包括通过Ca2+通量刺激。氟芬那酸,格列本脲,和钙调蛋白拮抗剂R24571,所有这些都以不同的方式阻断钙信号,在我们的实验模型中,所有抑制的5-LOX产物合成,表明钙介导的机制在eATP调节潜力中占主导地位。对嗜中性粒细胞粘附特性的研究表明,将fMLP添加到暴露于鼠伤寒沙门氏菌的嗜中性粒细胞时会形成细胞簇。与fMLP同时添加的eATP支持中性粒细胞极化和聚集。细胞来源的化学引诱物,如白三烯B4在募集额外的嗜中性粒细胞到组织损伤或病原体侵袭的病灶中起着至关重要的作用。和eATP,通过[Ca2+]i变化的动力学,在嗜中性粒细胞与鼠伤寒沙门氏菌相互作用过程中,fMLP诱导的白三烯合成中起着重要的决定性作用。
    Here, we demonstrate that human neutrophil interaction with the bacterium Salmonella typhimurium fuels leukotriene B4 synthesis induced by the chemoattractant fMLP. In this work, we found that extracellular ATP (eATP), the amount of which increases sharply during tissue damage, can effectively regulate fMLP-induced leukotriene B4 synthesis. The vector of influence strongly depends on the particular stage of sequential stimulation of neutrophils by bacteria and on the stage at which fMLP purinergic signaling occurs. Activation of 5-lipoxygenase (5-LOX), key enzyme of leukotriene biosynthesis, depends on an increase in the cytosolic concentration of Ca2+. We demonstrate that eATP treatment prior to fMLP, by markedly reducing the amplitude of the fMLP-induced Ca2+ transient jump, inhibits leukotriene synthesis. At the same time, when added with or shortly after fMLP, eATP effectively potentiates arachidonic acid metabolism, including by Ca2+ fluxes stimulation. Flufenamic acid, glibenclamide, and calmodulin antagonist R24571, all of which block calcium signaling in different ways, all suppressed 5-LOX product synthesis in our experimental model, indicating the dominance of calcium-mediated mechanisms in eATP regulatory potential. Investigation into the adhesive properties of neutrophils revealed the formation of cell clusters when adding fMLP to neutrophils exposed to the bacterium Salmonella typhimurium. eATP added simultaneously with fMLP supported neutrophil polarization and clustering. A cell-derived chemoattractant such as leukotriene B4 plays a crucial role in the recruitment of additional neutrophils to the foci of tissue damage or pathogen invasion, and eATP, through the dynamics of changes in [Ca2+]i, plays an important decisive role in fMLP-induced leukotrienes synthesis during neutrophil interactions with the bacterium Salmonella typhimurium.
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  • 文章类型: Journal Article
    自然杀伤(NK)细胞在感染早期对沙门氏菌感染的防御中起关键作用。我们先前的工作表明,A虫的排泄/分泌产物在体外抑制了NK活性。这里,我们询问家猪在与蛔虫和沙门氏菌血清型鼠伤寒合并感染期间,NK细胞功能是否受到影响。蛔虫共感染完全消除了沙门氏菌单感染猪的CD16CD8α穿孔素NK细胞中IL-12和IL-18驱动的IFN-γ产生升高。此外,蛔虫共感染阻止了沙门氏菌驱动的NK穿孔素水平和CD107a表面表达的升高。根据受损的效应器功能,单个和合并感染猪的NK细胞显示抑制性KLRA1和NKG2A受体基因的表达升高,与沙门氏菌单次感染期间NK细胞中激活的NKp46和NKp30受体的较高表达相反。这些差异伴随着A虫和A虫/沙门氏菌共感染的猪的NK细胞中T-bet蛋白表达的高度显著上调。一起,我们的数据强烈表明,蛔虫感染对NK功能的严重抑制,这可能会阻碍感染者对并发细菌感染的充分反应.
    Natural killer (NK) cells play a key role in defense against Salmonella infections during the early phase of infection. Our previous work showed that the excretory/secretory products of Ascaris suum repressed NK activity in vitro. Here, we asked if NK cell functionality was influenced in domestic pigs during coinfection with Ascaris and Salmonella enterica serotype Typhimurium. Ascaris coinfection completely abolished the IL-12 and IL-18 driven elevation of IFN-γ production seen in CD16 + CD8α + perforin + NK cells of Salmonella single-infected pigs. Furthermore, Ascaris coinfection prohibited the Salmonella-driven rise in NK perforin levels and CD107a surface expression. In line with impaired effector functions, NK cells from Ascaris-single and coinfected pigs displayed elevated expression of the inhibitory KLRA1 and NKG2A receptors genes, contrasting with the higher expression of the activating NKp46 and NKp30 receptors in NK cells during Salmonella single infection. These differences were accompanied by the highly significant upregulation of T-bet protein expression in NK cells from Ascaris-single and Ascaris/Salmonella coinfected pigs. Together, our data strongly indicate a profound repression of NK functionality by an Ascaris infection which may hinder infected individuals from adequately responding to a concurrent bacterial infection.
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