Immune defense

免疫防御
  • 文章类型: Editorial
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  • 文章类型: Journal Article
    本研究的目的是探讨褪黑素(MT)饲料补充对抗氧化能力的影响,免疫防御,和肠道菌群(P.clarkii)。六组克氏疟原虫饲喂含有不同水平MT的试验饲料:0mg/kg(对照),22.5、41.2、82.7、165.1和329.2mg/kg,持续2个月。具体增长率,肝细胞指数,在饲喂MT浓度为165.1mg/kg的虾的试验组中,条件因子最高。与对照组相比,补充高浓度MT的克拉氏疟原虫肝胰腺细胞的凋亡率较低。对肝胰腺中抗氧化能力和免疫反应相关酶的分析表明,饮食中补充MT可显着增强抗氧化系统和免疫反应。日粮中添加MT显著提高了抗氧化免疫相关基因的表达水平,降低了凋亡相关基因的表达水平。饮食MT与Firmicutes丰度的升高和肠道中变形杆菌丰度的降低有关;此外,导致有益细菌的丰度增加,如乳杆菌。虚线模型表明,适宜的MT浓度为154.09-157.09mg/kg。补充MT提高了克氏疟原虫的生长性能,对肠道微生物群产生积极影响,增强了免疫反应和抗病能力。因此,这项研究提供了有关在水产养殖领域中膳食MT补充剂应用的新观点。
    The aim of this study was to investigate the effects of melatonin (MT) feed supplementation on the antioxidant capacity, immune defense, and intestinal flora in Procambarus clarkii (P. clarkii). Six groups of P. clarkii were fed test feeds containing different levels of MT: 0 mg/kg (control), 22.5, 41.2, 82.7, 165.1, and 329.2 mg/kg for a duration of 2 months. The specific growth rate, hepatosomatic index, and condition factor were recorded highest in the test group of shrimp fed an MT concentration of 165.1 mg/kg. Compared to the control group, the rate of apoptosis was lower in hepatopancreas cells of P. clarkii supplemented with high concentrations of MT. Analyses of antioxidant capacity and immune-response-related enzymes in the hepatopancreas indicated that dietary supplementation of MT significantly augmented both the antioxidant system and immune responses. Dietary MT supplementation significantly increased the expression levels of antioxidant-immunity-related genes and decreased the expression levels of genes linked to apoptosis. Dietary MT was associated with an elevation in the abundance of the Firmicutes and a reduction in the abundance of the Proteobacteria in the intestines; besides, resulting in an increase in the abundance of beneficial bacteria, such as Lactobacilli. The broken-line model indicated that the suitable MT concentration was 154.09-157.09 mg/kg. MT supplementation enhanced the growth performance of P. clarkii, exerting a positive influence on the intestinal microbiota, and bolstered both immune response and disease resistance. Thus, this study offered novel perspectives regarding the application of dietary MT supplementation within the aquaculture field.
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  • 文章类型: Journal Article
    在本文中,对于2023系列的亮点,我们认为从单细胞RNA测序研究中对肥大细胞异质性和相互作用的理解越来越多。我们还讨论了有关肥大细胞与中枢神经系统相互作用的新概念,以及它们在宿主防御SARS-CoV-2感染中的作用的证据。
    In this article for the Highlights of 2023 Series, we consider the growing understanding of mast cell heterogeneity and interactions that has developed from single cell RNA sequencing studies. We also discuss novel concepts concerning mast cell interactions with the central nervous system and evidence for their role in host defense against SARS-CoV-2 infection.
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  • 文章类型: Journal Article
    在这项研究中,我们介绍了大嘴鲈鱼(Micropterussalmoides)中穿孔素(MsPRF1)的首次克隆和鉴定。MsPRF1的全长cDNA跨越1572个碱基对,编码由523个氨基酸组成的58.88kDa蛋白质。值得注意的是,该蛋白质包含MACPF和C2结构域。为了评估MsPRF1在各种健康的大嘴鲈鱼组织中的表达水平,采用实时定量PCR,揭示了肝脏和肠道中最高的表达。大嘴鲈鱼被诺卡氏菌感染后,MsPRF1的mRNA水平通常在48小时内增加。值得注意的是,重组蛋白MsPRF1对革兰氏阴性和革兰氏阳性细菌均表现出抑制作用。此外,在腹膜内注射rMsPRF1后,大嘴鲈鱼在N.seriolae攻击中显示出更高的存活率,并观察到组织细菌负荷的减少。此外,rMsPRF1对大口鲈鱼MO/MΦ细胞的吞噬和杀菌活性有显著影响,同时上调促炎因子的表达。这些结果表明,MsPRF1在大口鲈鱼对抗马尾藻感染的免疫反应中具有潜在作用。
    In this study, we present the first cloning and identification of perforin (MsPRF1) in largemouth bass (Micropterus salmoides). The full-length cDNA of MsPRF1 spans 1572 base pairs, encoding a 58.88 kDa protein consisting of 523 amino acids. Notably, the protein contains MACPF and C2 structural domains. To evaluate the expression levels of MsPRF1 in various healthy largemouth bass tissues, real-time quantitative PCR was employed, revealing the highest expression in the liver and gut. After the largemouth bass were infected by Nocardia seriolae, the mRNA levels of MsPRF1 generally increased within 48 h. Remarkably, the recombinant protein MsPRF1 exhibits inhibitory effects against both Gram-negative and Gram-positive bacteria. Additionally, the largemouth bass showed a higher survival rate in the N. seriolae challenge following the intraperitoneal injection of rMsPRF1, with observed reductions in the tissue bacterial loads. Moreover, rMsPRF1 demonstrated a significant impact on the phagocytic and bactericidal activities of largemouth bass MO/MΦ cells, concurrently upregulating the expression of pro-inflammatory factors. These results demonstrate that MsPRF1 has a potential role in the immune response of largemouth bass against N. seriolae infection.
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  • 文章类型: Journal Article
    无刺的蜜蜂Meliponascutellaris进行嗡嗡声授粉,有效地授粉几种具有经济相关性的野生植物和作物。然而,大多数研究都集中在蜜蜂上,在有关本地物种的研究中留下了巨大的空白,特别是关于农药组合对这些传粉媒介的影响。因此,本研究旨在评估吡虫啉(IMD)的亚致死作用,吡唑酮酯(PYR),和草甘膦(GLY)对黄藻的行为和脂肪体细胞形态和生理的影响。觅食者单独和联合口服暴露于不同的农药48小时。用污染溶液喂养的蜜蜂行走较少,移动速度较慢,呈现脂肪体的形态变化,包括空泡化,改变细胞形状和细胞核形态,并表现出更高的改变的卵母细胞和滋养细胞计数。在所有暴露的群体中,单独和组合,表达caspase-3的细胞数量增加,但与对照组相比,表达TLR4的细胞数量减少。与对照组相比,HSP70免疫标记的强度增加。然而,IMD中HSP90的免疫标记强度降低,GLY,和I+G(IMD+GLY)组,但在I+P暴露蜜蜂(IMD+PYR)中增加。或者,暴露于PYR和P+G(PYR+GLY)不影响免疫标记强度。我们的发现证明了分离和组合农药对重要的新热带传粉媒介的有害影响和环境后果。了解农药如何影响脂肪体可以为本地蜜蜂种群的整体健康和生存提供至关重要的见解,这可以帮助开发更环保的农业实践方法。
    The stingless bee Melipona scutellaris performs buzz pollination, effectively pollinating several wild plants and crops with economic relevance. However, most research has focused on honeybees, leaving a significant gap in studies concerning native species, particularly regarding the impacts of pesticide combinations on these pollinators. Thus, this study aimed to evaluate the sublethal effects of imidacloprid (IMD), pyraclostrobin (PYR), and glyphosate (GLY) on the behavior and fat body cell morphology and physiology of M. scutellaris. Foragers were orally exposed to the different pesticides alone and in combination for 48 h. Bees fed with contaminated solution walked less, moved slower, presented morphological changes in the fat body, including vacuolization, altered cell shape and nuclei morphology, and exhibited a higher count of altered oenocytes and trophocytes. In all exposed groups, alone and in combination, the number of cells expressing caspase-3 increased, but the TLR4 number of cells expressing decreased compared to the control groups. The intensity of HSP70 immunolabeling increased compared to the control groups. However, the intensity of the immunolabeling of HSP90 decreased in the IMD, GLY, and I + G (IMD + GLY) groups but increased in I + P-exposed bees (IMD + PYR). Alternatively, exposure to PYR and P + G (PYR + GLY) did not affect the immunolabeling intensity. Our findings demonstrate the hazardous effects and environmental consequences of isolated and combined pesticides on a vital neotropical pollinator. Understanding how pesticides impact the fat body can provide crucial insights into the overall health and survival of native bee populations, which can help develop more environmentally friendly approaches to agricultural practices.
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  • 文章类型: Journal Article
    埃及伊蚊传播脊椎动物病原体的能力取决于多种因素,包括蚊子的生活史特征,免疫反应,和微生物群(即,与蚊子一生相关的微生物)。小孢子虫Edhazardiaaedis是一种专性细胞内寄生虫,可特异性感染Ae。埃及伊蚊,严重影响蚊子的生存和其他对病原体传播至关重要的生活史特征。在这项工作中,我们调查了Ae中E.aedis如何影响粘质沙雷氏菌的细菌感染。埃及伊蚊.我们衡量了发展,生存,以及蚊子幼虫和成虫阶段的细菌负荷。在幼虫中,E.aedis暴露是水平的或垂直的,并且口服引入粘质链球菌。不管传播途径如何,E.aedis暴露导致幼虫中明显较高的粘质S.E.aedis暴露也显着降低幼虫的存活率,但随后暴露于粘质链球菌没有影响。在成年女性中,E.aedis暴露仅是水平的,并且口服或通过胸腔内注射引入粘质沙菌。在这两种情况下,E.aedis感染显着增加了成年雌性蚊子中的粘质链球菌细菌负荷。此外,感染了E.aedis并随后注射了粘质链球菌的女性死亡率为100%,这与细菌负荷的迅速增加相对应。这些发现表明,暴露于E.aedis可以影响蚊子中其他微生物的建立和/或复制。这对于理解蚊子免疫防御的生态学和蚊子媒介物种潜在的疾病传播具有意义。重要的是,小孢子虫Edhazardiaaedis是黄热病蚊子的寄生虫,埃及伊蚊.这种蚊子在美国和世界各地向人类传播多种病毒,包括登革热,黄热病,和寨卡病毒。全世界每年将有数亿人感染这些病毒之一。E.aedis感染显着降低了Ae的寿命。埃及伊蚊,因此是一种有前途的新型生物防治剂。这里,我们发现当蚊子被这种寄生虫感染时,它也更容易受到机会性细菌病原体的感染,粘质沙雷菌.这一新发现表明,蚊子控制其他微生物感染的能力受到寄生虫存在的影响。
    The ability of Aedes aegypti mosquitoes to transmit vertebrate pathogens depends on multiple factors, including the mosquitoes\' life history traits, immune response, and microbiota (i.e., the microbes associated with the mosquito throughout its life). The microsporidium Edhazardia aedis is an obligate intracellular parasite that specifically infects Ae. aegypti mosquitoes and severely affects mosquito survival and other life history traits critical for pathogen transmission. In this work, we investigated how E. aedis impacts bacterial infection with Serratia marcescens in Ae. aegypti mosquitoes. We measured development, survival, and bacterial load in both larval and adult stages of mosquitoes. In larvae, E. aedis exposure was either horizontal or vertical and S. marcescens was introduced orally. Regardless of the route of transmission, E. aedis exposure resulted in significantly higher S. marcescens loads in larvae. E. aedis exposure also significantly reduced larval survival but subsequent exposure to S. marcescens had no effect. In adult females, E. aedis exposure was only horizontal and S. marcescens was introduced orally or via intrathoracic injection. In both cases, E. aedis infection significantly increased S. marcescens bacterial loads in adult female mosquitoes. In addition, females infected with E. aedis and subsequently injected with S. marcescens suffered 100% mortality which corresponded with a rapid increase in bacterial load. These findings suggest that exposure to E. aedis can influence the establishment and/or replication of other microbes in the mosquito. This has implications for understanding the ecology of mosquito immune defense and potentially disease transmission by mosquito vector species.
    OBJECTIVE: The microsporidium Edhazardia aedis is a parasite of the yellow fever mosquito, Aedes aegypti. This mosquito transmits multiple viruses to humans in the United States and around the world, including dengue, yellow fever, and Zika viruses. Hundreds of millions of people worldwide will become infected with one of these viruses each year. E. aedis infection significantly reduces the lifespan of Ae. aegypti and is therefore a promising novel biocontrol agent. Here, we show that when the mosquito is infected with this parasite, it is also significantly more susceptible to infection by an opportunistic bacterial pathogen, Serratia marcescens. This novel discovery suggests the mosquito\'s ability to control infection by other microbes is impacted by the presence of the parasite.
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  • 文章类型: Journal Article
    坏死是先天性免疫所必需的一类促炎程序性坏死。受体相互作用蛋白激酶1/3(RIPK1/3)和底物混合谱系激酶结构域样蛋白(MLKL)是坏死轴的核心成分。鱼类坏死的激活和免疫功能仍然难以捉摸。在这里,我们研究了硬骨鱼副鱼中RIPK1/3(PoRIPK1/3)和MLKL(PoMLKL)的功能和激活。细菌感染增加了RIPK1/3和MLKL的表达。PoMLKL的N末端四螺旋束(4HB)结构域表现出细胞凋亡诱导活性,C末端假激酶结构域对4HB结构域具有自抑制作用。PoRIPK3能够磷酸化PoMLKLC末端结构域中的T360/S361残基并引发坏死,PoRIPK1增强了这种诱导坏死的活性。PoRIPK1/3与PoMLKL的相互作用依赖于RIP同型相互作用基序(RHIM),从PoRIPK1/3中删除RHIM导致PoRIPK1/3与PoMLKL解离。抑制PoMLKL介导的坏死增加了鱼类细胞和组织中的爱德华氏菌感染,并导致宿主的杀伤力显著增强。一起来看,这些结果揭示了PoRIPK1/3-PoMLKL信号通路的激活机制和坏死性凋亡在硬骨鱼免疫防御中的免疫功能。
    Necroptosis is a type of proinflammatory programmed necrosis essential for innate immunity. The receptor interacting protein kinases 1/3 (RIPK1/3) and the substrate mixed lineage kinase domain-like protein (MLKL) are core components of the necroptotic axis. The activation and immunological function of necroptosis in fish remain elusive. Herein, we studied the function and activation of RIPK1/3 (PoRIPK1/3) and MLKL (PoMLKL) in teleost Paralichthys olivaceus. Bacterial infection increased the expression of RIPK1/3 and MLKL. The N-terminal four-helix bundle (4HB) domain of PoMLKL exhibited necroptosis-inducing activity, and the C-terminal pseudokinase domain exerted auto-inhibitory effect on the 4HB domain. PoRIPK3 was capable of phosphorylating the T360/S361 residues in the PoMLKL C-terminal domain and initiated necroptosis, and this necroptosis-inducing activity was enhanced by PoRIPK1. PoRIPK1/3 interacted with PoMLKL in a manner that depended on the RIP homotypic interaction motif (RHIM), and deletion of RHIM from PoRIPK1/3 led to the dissociation of PoRIPK1/3 with PoMLKL. Inhibition of PoMLKL-mediated necroptosis increased Edwardsiella tarda infection in fish cells and tissues, and led to significantly enhanced lethality of the host. Taken together, these results revealed the activation mechanism of PoRIPK1/3-PoMLKL signaling pathway and the immunological function of necroptosis in the immune defense of teleost.
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  • 文章类型: Journal Article
    Serpin是丝氨酸蛋白酶抑制剂的蛋白质超家族。它们的功能之一是通过抑制酚氧化酶原的激活来参与免疫应答。为了阐明serpin在日本沼虾中的免疫作用,在这项研究中,从日本M.nipponense克隆了serpin基因(Mnserpin)。Mnserpin蛋白具有N端信号肽和含有铰链区的serpin结构域,serpin的签名序列和P1(精氨酸)-P1\'断裂键,在进化上与甲壳类昆虫密切相关。Mnserpin在肝胰腺和g中高度表达。Mnserpin表达在副溶血性弧菌和嗜水气单胞菌感染后先升高后降低,并通过dsMnserpin注射击倒,最大击倒效率为92%。Mnserpin敲除增加了夹域丝氨酸蛋白酶和酚氧化酶原基因的表达以及日本M.nipponense的酚氧化酶活性,以及副溶血性弧菌和嗜水菌感染后的死亡率。重组Mnserpin(rMnserpin)在体外显示出细菌结合和抑菌活性。此外,rMnserpin注射可降低副溶血性弧菌和嗜水性弧菌感染的细菌数量和死亡率。这些结果表明,Mnserpin在日本M.nipponense的先天免疫反应中起着重要作用。
    Serpins are a protein superfamily of serine protease inhibitors. One of their functions is to participate in immune responses by inhibiting the activation of prophenoloxidase. To elucidate the immune role of serpin in Macrobrachium nipponense, a serpin gene (Mnserpin) was cloned from M. nipponense in this study. Mnserpin protein has an N-terminal signal peptide and a serpin domain that contains a hinge region, a signature sequence of serpin and a P1(arginine)-P1\' scissile bond, and evolutionally closely related to the crustacean serpins. Mnserpin highly expressed in the hepatopancreas and gill. Mnserpin expression increased first and then decreased after Vibrio parahaemolyticus and Aeromonas hydrophila infection, and was knocked down by dsMnserpin injection with a maximum knockdown efficiency of 92 %. Mnserpin knockdown increased the expression of the clip domain serine protease and prophenoloxidase genes and phenoloxidase activity of M. nipponense as well as its mortality rate after V. parahaemolyticus and A. hydrophila infection. The recombinant Mnserpin (rMnserpin) showed bacteria-binding and bacteriostatic activity in vitro. Moreover, rMnserpin injection decreased the bacterial number and the mortality rate of M. nipponense post V. parahaemolyticus and A. hydrophila infection. These results suggested that Mnserpin plays a major role in the innate immune response of M. nipponense.
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  • 文章类型: Journal Article
    冬虫夏草在小金鸡中表现出超过5个月的营养生长。通过形态学观察和组学技术,阐明了中华青霉独特的发育过程;然而,关于宿主T.Xiaojinensis发生的变化的信息很少。RNA测序数据显示,当中华小孢子处于增殖阶段时,感染幼虫脂肪体的最大变化是选择性上调的免疫识别和抗菌肽基因。当中华小孢子处于静止阶段时,小金鸡的免疫途径恢复到正常水平,这与O.sinensis的成功定居相吻合。通路富集剖析显示,在此阶段,与能量代谢通路有关的基因表达量较高。代谢组学分析显示血淋巴中的氨基酸和脂质减少,而是在感染了O.sinensis后宿主幼虫的脂肪体内脂质的上调。我们提出了第一个与O感染的小金草代谢组研究整合的转录组。它将提高我们对宿主和昆虫病原真菌之间相互作用机制的理解,并促进未来对这些相互作用中涉及的基因和途径的功能研究。
    Ophiocordyceps sinensis exhibits more than 5 months of vegetative growth in Thitarodes xiaojinensis hemocoel. The peculiar development process of O. sinensis has been elucidated through morphological observation and omics technology; however, little information has been reported regarding the changes that occur in the host T. xiaojinensis. The RNA sequencing data showed that when O. sinensis blastospores were in the proliferative stage, the greatest change in the infected larval fat body was the selectively upregulated immune recognition and antimicrobial peptide genes. When O. sinensis blastospores were in the stationary stage, the immune pathways of T. xiaojinensis reverted to normal levels, which coincides with the successful settlement of O. sinensis. Pathway enrichment analysis showed a higher expression of genes involved in energy metabolism pathway in this stage. Metabolomic analyses revealed a reduction of amino acids and lipids in hemolymph, but an upregulation of lipids in the fat body of the host larvae after O. sinensis infection. We present the first transcriptome integrated with the metabolome study of T. xiaojinensis infected by O. sinensis. It will improve our understanding of the interaction mechanisms between the host and entomopathogenic fungi, and facilitate future functional studies of genes and pathways involved in these interactions.
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  • 文章类型: Journal Article
    淋巴结转移已被证明与许多癌症的预后呈正相关。然而,在临床治疗中,淋巴结清扫术并不总是成功的,提示肿瘤和前哨淋巴结中的免疫细胞在肿瘤免疫抑制中仍起着关键作用。最近的研究表明,肿瘤可以通过多种策略耐受免疫细胞,包括肿瘤诱导的巨噬细胞重编程,T细胞失活,B细胞致病性抗体的产生和调节性T细胞的激活,以促进肿瘤定植,增长,淋巴结转移。我们综述了免疫细胞在淋巴结转移过程中对抗肿瘤或促进癌细胞转移的双向作用。以及恶性癌细胞修饰免疫细胞的机制,为癌细胞的生长和存活创造更有利的环境。还讨论了针对淋巴结中免疫系统的研究和治疗策略以及淋巴结转移中潜在的免疫靶标。
    Lymph node metastasis has been shown to positively associated with the prognosis of many cancers. However, in clinical treatment, lymphadenectomy is not always successful, suggesting that immune cells in the tumor and sentinel lymph nodes still play a pivotal role in tumor immunosuppression. Recent studies had shown that tumors can tolerate immune cells through multiple strategies, including tumor-induced macrophage reprogramming, T cells inactivation, production of B cells pathogenic antibodies and activation of regulatory T cells to promote tumor colonization, growth, and metastasis in lymph nodes. We reviewed the bidirectional effect of immune cells on anti-tumor or promotion of cancer cell metastasis during lymph node metastasis, and the mechanisms by which malignant cancer cells modify immune cells to create a more favorable environment for the growth and survival of cancer cells. Research and treatment strategies focusing on the immune system in lymph nodes and potential immune targets in lymph node metastasis were also be discussed.
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