helminth infection

蠕虫感染
  • 文章类型: Journal Article
    两项研究定义了簇绒细胞乙酰胆碱如何促进寄生虫排出。Billip等人。证明乙酰胆碱增加水的分泌,以促进“哭泣”响应。Ndjim等人。发现簇绒细胞乙酰胆碱对蠕虫的繁殖力有直接影响。当稀有簇细胞变得丰富时,这两个过程仅在重塑的上皮中有效。
    Two studies defined how tuft cell acetylcholine promotes parasite expulsion. Billip et al. demonstrated that acetylcholine increases water secretion, to promote the \'weep\' response. Ndjim et al. found that tuft cell acetylcholine has a direct effect on worm fecundity. Both processes are only effective in the remodeled epithelium when the rare tuft cells have become abundant.
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  • 文章类型: Journal Article
    上皮细胞分泌氯化物调节粘膜屏障的水释放,支持稳态水合和“哭泣”反应,这对于2型免疫防御寄生虫(蠕虫)至关重要。小肠中的上皮簇细胞感知蠕虫并释放细胞因子和脂质以激活2型免疫细胞,但它们是否调节上皮分泌尚不清楚。这里,我们发现,簇绒细胞活化迅速诱导小肠上皮氯化物分泌。这种反应需要簇绒细胞感觉功能和簇绒细胞衍生的乙酰胆碱(ACh),直接作用于邻近的上皮细胞以刺激氯化物分泌,独立于神经元。最大簇绒细胞诱导的氯化物分泌与蠕虫的免疫限制相吻合,在缺乏簇绒细胞来源的ACh的小鼠中,清除延迟,尽管正常的2型炎症。因此,我们发现了一个上皮固有反应单元,该单元使用ACh将簇绒细胞感应与相邻上皮细胞的分泌防御相耦合。
    Epithelial cells secrete chloride to regulate water release at mucosal barriers, supporting both homeostatic hydration and the \"weep\" response that is critical for type 2 immune defense against parasitic worms (helminths). Epithelial tuft cells in the small intestine sense helminths and release cytokines and lipids to activate type 2 immune cells, but whether they regulate epithelial secretion is unknown. Here, we found that tuft cell activation rapidly induced epithelial chloride secretion in the small intestine. This response required tuft cell sensory functions and tuft cell-derived acetylcholine (ACh), which acted directly on neighboring epithelial cells to stimulate chloride secretion, independent of neurons. Maximal tuft cell-induced chloride secretion coincided with immune restriction of helminths, and clearance was delayed in mice lacking tuft cell-derived ACh, despite normal type 2 inflammation. Thus, we have uncovered an epithelium-intrinsic response unit that uses ACh to couple tuft cell sensing to the secretory defenses of neighboring epithelial cells.
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  • 文章类型: Journal Article
    针对肠蠕虫的保护性免疫需要诱导由各种细胞和可溶性效应子协调的强大的2型免疫,这些效应子促进杯状细胞增生,粘液产生,上皮增殖,和平滑肌收缩以排出蠕虫并重新建立免疫稳态。相反,2型免疫缺陷导致无效的蠕虫清除,持续性感染,和炎症。巨噬细胞是高度可塑性的细胞,在蠕虫感染期间获得交替活化状态,但是以前被证明对Trichurismuris感染的抵抗力是可有可无的。
    我们使用体内小鼠模型A20myel-KO,其特征是在骨髓细胞中特异性缺失有效的抗炎因子A20(TNFAIP3),过度的1型细胞因子产生,和自发性关节炎的发展。我们用胃肠道蠕虫Trichurismuris感染A20myel-KO小鼠,并分析了先天和适应性反应。我们对分选的骨髓细胞进行RNA测序,以研究A20对巨噬细胞极化和2型免疫的作用。此外,我们在A20myel-KO小鼠中评估了1型细胞因子途径对蠕虫清除和鼠伤寒沙门氏菌感染的药理学抑制作用。
    我们表明,适当的巨噬细胞极化对于清除蠕虫至关重要,我们确定A20是诱导针对毛虫的2型免疫反应的必需髓样因子。A20myel-KO小鼠的特征在于持续的毛虫感染和肠道炎症。髓样A20缺乏诱导强经典巨噬细胞极化,阻碍抗蠕虫2型免疫激活;然而,它促进有害的Th1/Th17反应。抗体介导的1型细胞因子IFN-γ的中和,IL-18和IL-12在A20myel-KO小鼠中预防骨髓协调的Th1极化并重建2型介导的针对T.muris的保护性免疫。相比之下,A20myel-KO小鼠的强Th1偏向性免疫提供了对抗鼠伤寒沙门氏菌感染的保护。
    我们在此确定A20是响应于蠕虫和肠道细菌感染的正确巨噬细胞极化和适当的适应性粘膜免疫的关键髓样因子。
    UNASSIGNED: Protective immunity against intestinal helminths requires induction of robust type-2 immunity orchestrated by various cellular and soluble effectors which promote goblet cell hyperplasia, mucus production, epithelial proliferation, and smooth muscle contractions to expel worms and re-establish immune homeostasis. Conversely, defects in type-2 immunity result in ineffective helminth clearance, persistent infection, and inflammation. Macrophages are highly plastic cells that acquire an alternatively activated state during helminth infection, but they were previously shown to be dispensable for resistance to Trichuris muris infection.
    UNASSIGNED: We use the in vivo mouse model A20myel-KO, characterized by the deletion of the potent anti-inflammatory factor A20 (TNFAIP3) specifically in the myeloid cells, the excessive type-1 cytokine production, and the development of spontaneous arthritis. We infect A20myel-KO mice with the gastrointestinal helminth Trichuris muris and we analyzed the innate and adaptive responses. We performed RNA sequencing on sorted myeloid cells to investigate the role of A20 on macrophage polarization and type-2 immunity. Moreover, we assess in A20myel-KO mice the pharmacological inhibition of type-1 cytokine pathways on helminth clearance and the infection with Salmonella typhimurium.
    UNASSIGNED: We show that proper macrophage polarization is essential for helminth clearance, and we identify A20 as an essential myeloid factor for the induction of type-2 immune responses against Trichuris muris. A20myel-KO mice are characterized by persistent Trichuris muris infection and intestinal inflammation. Myeloid A20 deficiency induces strong classical macrophage polarization which impedes anti-helminth type-2 immune activation; however, it promotes detrimental Th1/Th17 responses. Antibody-mediated neutralization of the type-1 cytokines IFN-γ, IL-18, and IL-12 prevents myeloid-orchestrated Th1 polarization and re-establishes type-2-mediated protective immunity against T. muris in A20myel-KO mice. In contrast, the strong Th1-biased immunity in A20myel-KO mice offers protection against Salmonella typhimurium infection.
    UNASSIGNED: We hereby identify A20 as a critical myeloid factor for correct macrophage polarization and appropriate adaptive mucosal immunity in response to helminth and enteric bacterial infection.
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  • 文章类型: Case Reports
    包虫病是由寄生虫细粒棘球蚴引起的人畜共患疾病。它是世界许多地方的地方病。尽管人类是寄生虫的附带宿主,这种疾病有时会导致致命的后果。肝和肺是人类最常见的感染部位。我们报告了一名45岁的女性,她主诉右侧的软骨痛,发烧,咳嗽,最初怀疑是肝脓肿,但后来诊断为肝脏巨大钙化包虫囊肿。细粒棘球蚴的影像学和免疫球蛋白G有助于确认我们的诊断。根据她的症状,患者接受了镇痛药的对症治疗,扑热息痛,和止咳止咳,发烧,咳嗽,分别。就确定性护理而言,她接受了口服阿苯达唑治疗,并转诊到她的家乡进行必要的手术干预。
    Hydatid disease is a zoonotic disease caused by the parasite Echinococcus granulosus. It is an endemic disease in many parts of the world. Although humans are incidental hosts of the parasite, the disease sometimes results in fatal consequences. The liver and lungs are the most common sites of infection in humans. We report the case of a 45-year-old female who presented with complaints of right hypochondriac pain, fever, and cough, initially suspected as a case of liver abscess but later diagnosed as a giant calcified hydatid cyst of the liver. Imaging and immunoglobulin G for Echinococcus granulosus helped confirm our diagnosis. Based on her symptoms, the patient was treated symptomatically with analgesics, paracetamol, and an antitussive for pain, fever, and cough, respectively. In terms of definitive care, she was treated with oral albendazole and referred to her home district for necessary surgical intervention.
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  • 文章类型: Case Reports
    我们描述了一个34岁妇女的独特案例,该妇女在过去一个月内向急诊科提出呼吸困难和胸痛的投诉。较早的紧急护理访视的胸部X射线(CXR)担心左肺有大量液体混浊,随访成像显示有可疑的肺囊性脓肿的囊性肿块。患者接受了完整的肺叶切除术和切除术。手术后活检证实肺包虫囊性肿块和破裂或接种到肝组织的迹象。患者接受辅助治疗后出院,并建议在接下来的十年中进行影像学随访。诊断,治疗,本报告讨论了维护指南,鉴于缺乏关于包虫病的完整文献,该报告揭示了专家之间的争议。我们提出此病例的目的是在美国提出罕见的肺包虫病诊断,并强调早期影像学和诊断以防止囊性破裂和继发器官播散的重要性。
    We depict a unique case of a 34-year-old woman who presents to the emergency department with complaints of dyspnea and chest pain for the past month. A chest x-ray (CXR) from an earlier urgent care visit was concerning for large fluid opacity in the left lung and follow-up imaging revealed a cystic mass suspicious of a pulmonary cystic abscess. The patient underwent complete lobectomy and resection. Post-surgical biopsy confirmed pulmonary hydatid cystic mass and signs of rupture or seeding to liver tissue. The patient was discharged with adjuvant therapy and recommended imaging follow-up for the next decade. The diagnosis, treatment, and maintenance guidelines are discussed in this report which reveals controversy between experts given the lack of complete literature regarding echinococcosis. Our purpose in putting forward this case is to present a rare diagnosis of pulmonary echinococcosis in the United States and to emphasize the importance of early imaging and diagnosis to prevent cystic rupture and secondary organ dissemination.
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  • 文章类型: Journal Article
    为了确定IL-4/IL13受体在交替激活的巨噬细胞(AAM或M2)的发育中的作用,以及它们在调节对蠕虫寄生虫的肠外阶段的免疫力中的作用,我们追踪了缺乏IL-4Rα基因的小鼠品系(IL-4Rα-/-)和巨噬细胞/中性粒细胞特异性IL-4Rα缺陷型小鼠品系(LysMcreIL-4Rα-/lox或cre/LoxP)的感染.而100%的T.crassiceps感染的IL-4Rα/(WT)小鼠携带大量寄生虫,超过50%的eIL-4Rα-/-小鼠解决了感染。大约88%的LysMcreIL-4Rα-/lox小鼠表现出对感染的灭菌免疫。其余几只受感染的cre/LoxP小鼠在其腹膜腔中显示出最低数量的幼虫。WT小鼠无法控制感染与抗原特异性Th2型反应相关,具有较高水平的IgG1,IL-4,IL-13和总IgE,减少NO产生,和增加的精氨酸酶活性。相比之下,IL-4Rα-/-半抗性小鼠显示Th1/Th2组合应答。此外,来自WT小鼠的巨噬细胞显示出更高的精氨酸酶-1和RELM-α转录本,以及与抗CD3/CD28刺激的T细胞相比具有强大抑制活性的PD-L2的表达增加;所有这些特征都与AAM或M2巨噬细胞表型相关。相比之下,IL-4Rα-/-和LysMcreIL-4Rα-/lox小鼠均未完全发展AAM或显示对CD3/CD28刺激的T细胞的抑制活性,减少PDL2表达。此外,T-CD8+但无T-CD4+细胞显示抑制表型,在WT和IL-4Rα-/-中Tim-3和PD1表达增加,在T.crassiceps感染的LysMcreIL-4Rα-/lox小鼠中不存在。这些发现证明了IL-4信号通路在囊虫病期间维持AAM及其抑制活性中的关键作用。提示AAM在有利于T.crusiceps感染的易感性中的关键作用。因此,这些抑制细胞的缺失是成功控制实验性囊虫病的主要机制之一。
    To determine the role that the IL-4/IL13 receptor plays in the development of alternatively activated macrophages (AAM or M2) and their role in the regulation of immunity to the extraintestinal phase of the helminth parasite Taenia crassiceps, we followed the infection in a mouse strain lacking the IL-4Rα gene (IL-4Rα-/-) and in the macrophage/neutrophil-specific IL-4Rα-deficient mouse strain (LysMcreIL-4Rα-/lox or cre/LoxP). While 100% of T. crassiceps-infected IL-4Rα+/+ (WT) mice harbored large parasite loads, more than 50% of th eIL-4Rα-/- mice resolved the infection. Approximately 88% of the LysMcreIL-4Rα-/lox mice displayed a sterilizing immunity to the infection. The remaining few infected cre/LoxP mice displayed the lowest number of larvae in their peritoneal cavity. The inability of the WT mice to control the infection was associated with antigen-specific Th2-type responses with higher levels of IgG1, IL-4, IL-13, and total IgE, reduced NO production, and increased arginase activity. In contrast, IL-4Rα-/- semi-resistant mice showed a Th1/Th2 combined response. Furthermore, macrophages from the WT mice displayed higher transcripts for Arginase-1 and RELM-α, as well as increased expression of PD-L2 with robust suppressive activity over anti-CD3/CD28 stimulated T cells; all of these features are associated with the AAM or M2 macrophage phenotype. In contrast, both the IL-4Rα-/- and LysMcreIL-4Rα-/lox mice did not fully develop AAM or display suppressive activity over CD3/CD28 stimulated T cells, reducing PDL2 expression. Additionally, T-CD8+ but no T-CD4+ cells showed a suppressive phenotype with increased Tim-3 and PD1 expression in WT and IL-4Rα-/-, which were absent in T. crassiceps-infected LysMcreIL-4Rα-/lox mice. These findings demonstrate a critical role for the IL-4 signaling pathway in sustaining AAM and its suppressive activity during cysticercosis, suggesting a pivotal role for AAM in favoring susceptibility to T. crassiceps infection. Thus, the absence of these suppressor cells is one of the leading mechanisms to control experimental cysticercosis successfully.
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  • 文章类型: Journal Article
    能量和营养需求在塑造渗透到肿瘤和寄生虫感染部位的免疫细胞中起着至关重要的作用。免疫细胞和微环境之间的动态相互作用,无论是在肿瘤还是蠕虫感染的情况下,对于理解免疫极化的机制和制定策略来操纵它们以促进可以帮助治疗这些疾病的功能性和有效的免疫反应至关重要。在这次审查中,我们概述了在肿瘤发生和蠕虫感染建立过程中引发的免疫反应,在这两种情况下都突出了向慢性病的过渡。我们讨论了在正常条件下以及存在肿瘤和蠕虫的情况下免疫细胞的能量需求。此外,我们比较了肿瘤微环境和感染部位发生的代谢变化,强调诱导的改变重新定向免疫反应,从而促进癌细胞或蠕虫的存活。这一新兴学科为疾病发病机理提供了宝贵的见解。我们还提供了通过靶向塑造免疫表型的代谢途径来增强免疫活性的新策略的例子,目的是在癌症和蠕虫感染中取得积极成果。
    Energetic and nutritional requirements play a crucial role in shaping the immune cells that infiltrate tumor and parasite infection sites. The dynamic interaction between immune cells and the microenvironment, whether in the context of tumor or helminth infection, is essential for understanding the mechanisms of immunological polarization and developing strategies to manipulate them in order to promote a functional and efficient immune response that could aid in the treatment of these conditions. In this review, we present an overview of the immune response triggered during tumorigenesis and establishment of helminth infections, highlighting the transition to chronicity in both cases. We discuss the energetic demands of immune cells under normal conditions and in the presence of tumors and helminths. Additionally, we compare the metabolic changes that occur in the tumor microenvironment and the infection site, emphasizing the alterations that are induced to redirect the immune response, thereby promoting the survival of cancer cells or helminths. This emerging discipline provides valuable insights into disease pathogenesis. We also provide examples of novel strategies to enhance immune activity by targeting metabolic pathways that shape immune phenotypes, with the aim of achieving positive outcomes in cancer and helminth infections.
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  • 文章类型: Journal Article
    免疫发育受到垂直转移线索的深刻影响。然而,关于母体先天样淋巴细胞如何调节子代免疫,人们知之甚少。这里,我们表明,从γδT细胞缺陷(TCRδ-/-)大坝出生的小鼠表现出第一次呼吸诱导的炎症增加,具有选择性富含2型细胞因子和2型极化免疫细胞的肺环境,与γδT细胞充足的大坝的后代相比。蠕虫感染后,从TCRδ-/-大坝出生的小鼠维持增加的2型炎症反应。这与幼崽的基因型无关。相反,TCRδ-/-水坝的后代拥有独特的肠道微生物群,在出生和寄养期间获得,和肠道短链脂肪酸(SCFA)的水平降低,如戊酸酯和己酸酯。重要的是,外源性SCFA补充剂抑制2型先天淋巴细胞功能,并抑制首次呼吸和感染诱导的炎症.一起来看,我们的发现揭示了母体γδT细胞-微生物群-SCFA轴调节新生儿肺免疫。
    Immune development is profoundly influenced by vertically transferred cues. However, little is known about how maternal innate-like lymphocytes regulate offspring immunity. Here, we show that mice born from γδ T cell-deficient (TCRδ-/-) dams display an increase in first-breath-induced inflammation, with a pulmonary milieu selectively enriched in type 2 cytokines and type 2-polarized immune cells, when compared with the progeny of γδ T cell-sufficient dams. Upon helminth infection, mice born from TCRδ-/- dams sustain an increased type 2 inflammatory response. This is independent of the genotype of the pups. Instead, the offspring of TCRδ-/- dams harbors a distinct intestinal microbiota, acquired during birth and fostering, and decreased levels of intestinal short-chain fatty acids (SCFAs), such as pentanoate and hexanoate. Importantly, exogenous SCFA supplementation inhibits type 2 innate lymphoid cell function and suppresses first-breath- and infection-induced inflammation. Taken together, our findings unravel a maternal γδ T cell-microbiota-SCFA axis regulating neonatal lung immunity.
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  • 文章类型: Journal Article
    肠道是一个强大的消化系统和最复杂的免疫器官之一。证据表明,簇绒细胞(TC),一种具有独特形态特征的上皮细胞,在各种生理过程中发挥重要作用。根据不同的分子标准,TC可以广泛地分为不同的亚型。在这次审查中,我们讨论了其生物学特性和在维持胃肠道稳态中的作用。我们还强调其与免疫系统的相关性,并强调其对肠道疾病的强大影响,包括炎症和肿瘤.此外,我们为未来与TC相关的临床诊断和治疗策略提供了新的见解.
    The intestine is a powerful digestive system and one of the most sophisticated immunological organs. Evidence shows that tuft cells (TCs), a kind of epithelial cell with distinct morphological characteristics, play a significant role in various physiological processes. TCs can be broadly categorized into different subtypes depending on different molecular criteria. In this review, we discuss its biological properties and role in maintaining homeostasis in the gastrointestinal tract. We also emphasize its relevance to the immune system and highlight its powerful influence on intestinal diseases, including inflammations and tumors. In addition, we provide fresh insights into future clinical diagnostic and therapeutic strategies related to TCs.
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  • 文章类型: Journal Article
    靶向选择性治疗(TST)是减少驱虫药的使用并延迟抗性线虫种群发展的替代方法。然而,关于这种治疗对牲畜生产力的实际影响的信息有限。这项研究的目的是评估在TST下自然感染胃肠线虫(GIN)的SantaInes(头发)和IledeFrance(羊毛)羔羊的生产性能,该TST基于压积细胞体积(PCV)与抑制性驱虫治疗。将38只羔羊分为两个治疗组:抑制治疗,每两周用monepantel和TST浸透动物,当动物出现PCV≤20%时,用相同的驱虫药治疗。粪便,血,每周测量体重,以确定每克粪便中的鸡蛋,PCV,血浆总蛋白,和体重增加。动物被宰杀后,将屠体称重以确定屠体产量。在TST组中,与相应的体重相比,在羊毛中观察到约21.3%的生产损失和在毛羔羊中的25.9%的生产损失。在实验期间,血液学变量发生了显着差异,尤其是在TST下的羊毛羔羊中。有利的环境条件使感染性幼虫能够在牧场上生存和茁壮成长。在法兰西岛羔羊和圣伊内斯羔羊中发现的最常见的寄生虫是扭曲的Haemonchuscontortus和肠道线虫,分别。虽然TST可以预防死亡,它没有防止生产损失。由于GIN寄生,两个品种的产量均显着下降。
    Targeted selective treatment (TST) is an alternative method to reduce the use of anthelmintics and delay the development of resistant nematode populations. However, there is limited information on the actual effects of this type of treatment on livestock productivity. The objective of this study was to evaluate the production performance of Santa Ines (hair) and Ile de France (wool) lambs naturally infected with gastrointestinal nematodes (GIN) under TST based on packed cell volume (PCV) versus suppressive anthelmintic treatments. Thirty-eight lambs were divided into two treatment groups: Suppressive treatment, animals were drenched with monepantel every two weeks and TST, animals were treated with the same anthelmintic when they presented PCV ≤ 20%. Feces, blood, and weight were measured weekly to determine eggs per gram of feces, PCV, total plasma protein, and weight gain. After animals were slaughtered, carcasses were weighed to determine carcass yield. In the TST group, substantial productive losses of approximately 21.3% in the wool and 25.9% in the hair lambs were observed in body weight compared to their counterparts. Significant differences in hematological variables occurred over the experimental period, especially in the wool lambs under TST. Favorable environmental conditions enabled infective larvae to survive and thrive on pasture. Haemonchus contortus and intestinal nematodes were the most common parasites found in the Ile de France lambs and the Santa Ines lambs, respectively. Although TST prevented mortality, it did not prevent production losses. Both breeds showed a significant drop in production due to GIN parasitism.
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