蠕虫及其衍生物对过敏性疾病的抑制作用

蠕虫感染极为普遍,全球大约有1／4人口感染,世界各地均有分布,尤其是热带农村地区的流行率最高。蠕虫病主要表现为：嗜酸性粒细胞增多,血清抗体水平增高,速发型皮肤过敏反应等。但随着蠕虫与宿主长期协同演化,二者之间不再是一味的损伤,近些年来大量流行病学调查和动物实验研究显示：部分蠕虫及其衍生物能够抑制过敏性疾病的发生发展。本文就其免疫机制及几种蠕虫在过敏性疾病中作用的研究进行综述。     

益生菌防治过敏性疾病的进展和展望

过敏是一种病理性的免疫反应。随着全球患病率逐年上升,它已成为困扰人类健康的常见疾病。目前针对过敏性疾病的疗法大都收效甚微。研究证实,益生菌可以刺激免疫细胞的免疫调节特性,维持免疫内环境平衡,调节胃肠道生态系统,是潜在的防治过敏性疾病的有效疗法。改变抗原提呈细胞的功能或调节Th1/Th2平衡是益生菌抗过敏的基本作用机制。目前益生菌防治过敏性疾病已经成为国内外研究的热点,未来有望利用益生菌实现过敏性疾病的个性化与精准化治疗。本文就益生菌防治过敏性疾病的最新进展以及该领域前沿作一综述,期望有助于我国益生菌治疗和预防过敏性疾病的普及和研究。     

肠道菌群与过敏性疾病

近年有关过敏性疾病的流行病学调查、粪便菌群分析和临床研究提示,过敏性疾病的发生与发展与早期肠道菌群的紊乱有密切的关联性。1过敏性疾病概述过敏性疾病(又称变态反应性疾病)被世界卫生组织(WHO)认为是当今世界性的重大卫生学问题。过敏性疾病主要包括变应性鼻炎、过敏性结     

肠道菌群与婴幼儿过敏性疾病

肠道菌群是一个被遗忘的"器官",其在宿主消化营养免疫发育等诸多方面发挥着极为重要的作用。0~3岁是婴幼儿肠道菌群建立的关键时间窗,其与肠道免疫系统的成熟同步,是形成免疫耐受的关键时期,如果这一时期肠道菌群发生紊乱,可导致免疫耐受破坏,引起婴幼儿过敏性疾病。近年来流行病学调查和实验研究提示婴幼儿早期肠道菌群紊乱与过敏性疾病的发生发展密切相关,本研究就婴幼儿常见过敏性疾病如特应性皮炎、食物过敏、哮喘、过敏性鼻炎等与肠道菌群的相关性进行综述。     

肠道微生物与过敏性疾病关系研究进展

目前,过敏性疾病的防治主要依赖于使用抗生素,然而抗生素的滥用已造成了严重的危害。近年来随着肠道微生物相关研究的不断深入以及人们对过敏性疾病的日益关注与重视,肠道微生物与过敏性疾病间的关系逐渐受到科学家们的关注。调整肠道菌群结构可能为过敏性疾病的防治提供新的思路。目前对肠道微生物与过敏性疾病间的相关性报道相对较少且未有深层次的剖析。本文总结了关于肠道微生物与过敏性疾病关系的研究起源、发展与现状,旨在为过敏性疾病的防治提供新策略。     

过敏性眼表疾病的临床分析

目的探讨过敏性眼表疾病(AOD)患者的临床特征和规律,以进一步提高诊疗水平。方法对我院诊治的200例AOD患者的临床资料进行综合分析比较。结果 (1)AOD主要表现为过敏性结膜炎,分别是季节性和常年性,二者比例分别为41.0%和45.0%;(2)眼痒(92.0%)和结膜充血(93.0%)是AOD最常见的症状和体征;(3)常年性过敏性结膜炎诊断符合率为48.8%,显著低于其他AOD分型患者(P<0.01)。结论明确AOD的临床特征是提高诊治的前提。     

过敏性眼表疾病的临床特点及诊治研究

目的:对过敏性眼表疾病的临床特点和相关的诊治方法进行分析探讨.方法:选取100例过敏性眼表疾病的患者,对其相应的临床资料进行回顾性分析、通过对过敏性眼表疾病的病史、症状、体征等临床特点进行统计,进而对诊治方法进行分析探讨.结果:50例患者有过敏性眼病史,90例患者表现为眼痒,89例患者表现有异物感,88例患者表现为结膜充血,76例患者表现有上眼睑结膜乳头,70例患者表现有上眼睑结膜滤泡.45例患者为常年过敏性结膜炎,30例患者为特异性结膜炎,10例患者为巨乳头结膜炎,80例患者为过敏性结膜炎,嗜酸性粒细胞的阳性率为100％.经过治疗后,57例患者得到缓解,7例患者得到明显改善,30例患者病情得到控制,且有9例重症患者在急性期应用了激素治疗,6例患者临床症状无明显改善.结论:过敏性眼表疾病的临床症状表现差异较大,对过敏性眼表疾病患者的临床特点做出准确的判断并给出正确及时的治疗,对过敏性眼表疾病患者的恢复有一定的临床意义.     

高脂肪饮食对益生菌缓解大鼠过敏性炎症作用的影响及意义

目的 探究高脂肪饮食对过敏性炎症的发生以及对益生菌缓解大鼠过敏性炎症效果的影响及其机制。方法 将3周离乳期雄性Wistar大鼠（57 g±9 g）随机分为5组（8只/组）：对照组、正常饮食模型组、正常饮食治疗组、高脂肪饮食模型组及高脂肪饮食治疗组。基于正常饮食和高脂肪饮食分别建立大鼠过敏性炎症模型,应用益生菌对不同饮食的模型组大鼠进行干预,观察应用益生菌治疗后各组大鼠的过敏体征、炎症细胞及免疫平衡的变化,同时应用变性凝胶梯度电泳对各组大鼠的肠道菌群进行初步分析。结果 相较于正常饮食模型组,高脂肪饮食模型组大鼠过敏体征加重,血中炎症细胞水平增高,Th1/Th2失衡显著（t=-8.563,P=0.005）,肠道菌群多样性显著降低。益生菌能缓解过敏性炎症大鼠的过敏体征,使炎症细胞浸润减轻,明显纠正血和鼻灌洗液中Th1/Th2失衡（t=3.778、10.451,P=0.027、0.001）,恢复肠道菌群多样性。而在益生菌缓解过敏性炎症时伴有高脂肪饮食能阻碍过敏体征的缓解,加重炎症细胞的浸润,延缓了益生菌对血清中Th1/Th2的纠偏作用（t=-10.157,P=0.001）,阻碍了益生菌对肠道菌...     

肠道菌群与过敏性哮喘

近年来随着过敏性哮喘发病率的持续升高,人们开始注意到环境、生活方式的改变可能会影响过敏性哮喘的发生。流行病学调查显示,过敏性哮喘的发生和发展与生命早期肠道菌群的紊乱密切相关。本研究主要综述近年来肠道菌群对过敏性哮喘发生的影响及机制,探讨影响肠道菌群定植的主要因素,以及微生态调节剂在过敏性哮喘等变应性疾病中的预防和治疗作用。     

IL-18与过敏性疾病

IL-18属IL-1家族成员,最初被命名为IFN—γ诱导因子。一般认为参与Th1型应答,在IL-12共同作用下,IL-18强烈诱导Th1型细胞因予的产生,如IFN—γ、TNF-α,导致组织损伤。然而,IL-18在一定的条件下也能诱导Th2型免疫应答,它能直接刺激肥大细胞、嗜碱性粒细胞产生IL-4,释放组胺;在IL-2的协助下,刺激NK细胞和T细胞产生更多IL-4和IL-13,诱导B细胞产生IgE,在过敏性疾病炎症反应中起着重要作用。     

Immune Antibodies and Helminth Products Drive CXCR2-Dependent Macrophage-Myofibroblast Crosstalk to Promote Intestinal Repair

Helminth parasites can cause considerable damage when migrating through host tissues, thus making rapid tissue repair imperative to prevent bleeding and bacterial dissemination particularly during enteric infection. However, how protective type 2 responses targeted against these tissue-disruptive multicellular parasites might contribute to homeostatic wound healing in the intestine has remained unclear. Here, we observed that mice lacking antibodies (Aid^-/-) or activating Fc receptors (Fcrg^-/-) displayed impaired intestinal repair following infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb), whilst transfer of immune serum could partially restore chemokine production and rescue wound healing in Aid^-/- mice. Impaired healing was associated with a reduced expression of CXCR2 ligands (CXCL2/3) by macrophages (MΦ) and myofibroblasts (MF) within intestinal lesions. Whilst antibodies and helminths together triggered CXCL2 production by MΦ in vitro via surface FcR engagement, chemokine secretion by intestinal MF was elicited by helminths directly via Fcrg-chain/dectin2 signaling. Blockade of CXCR2 during Hpb challenge infection reproduced the delayed wound repair observed in helminth infected Aid^-/- and Fcrg^-/- mice. Finally, conditioned media from human MΦ stimulated with infective larvae of the helminth Ascaris suum together with immune serum, promoted CXCR2-dependent scratch wound closure by human MF in vitro. Collectively our findings suggest that helminths and antibodies instruct a chemokine driven MΦ-MF crosstalk to promote intestinal repair, a capacity that may be harnessed in clinical settings of impaired wound healing.     

The Effect of Maternal Helminth Infection on Maternal and Neonatal Immune Function and Immunity to Tuberculosis

Background

M. tuberculosis and helminth infection each affects one third of the world population. Helminth infections down regulate cell mediated immune responses and this may contribute to lower efficacy of BCG vaccination and higher prevalence of tuberculosis.

Objective

To determine the effect of maternal helminth infection on maternal and neonatal immune function and immunity to TB.

Methods

In this cross sectional study, eighty five pregnant women were screened for parasitic and latent TB infections using Kato-Katz and QFT-GIT tests, respectively. IFN-γ and IL-4 ELISpot on Cord blood Mononuclear Cells, and total IgE and TB specific IgG ELISA on cord blood plasma was performed to investigate the possible effect of maternal helminth and/or latent TB co-infection on maternal and neonatal immune function and immunity to TB.

Result

The prevalence of helminth infections in pregnant women was 27% (n = 23), with Schistosoma mansoni the most common helminth species observed (20% of women were infected). Among the total of 85 study participants 25.8% were QFT-GIT positive and 17% had an indeterminate result. The mean total IgE value of cord blood was significantly higher in helminth positive than negative women (0.76 vs 0.47, p = 0.042). Cross placental transfer of TB specific IgG was significantly higher in helminth positive (21.9±7.9) than negative (12.3±5.1), p = 0.002) Latent TB Infection positive participants. The IFN-γ response of CBMCs to ESAT-6/CFP-10 cocktail (50 vs 116, p = 0.018) and PPD (58 vs 123, p = 0.02) was significantly lower in helminth positive than negative participants. There was no significant difference in IL-4 response of CBMCs between helminth negative and positive participants.

Conclusions

Maternal helminth infection had a significant association with the IFN-γ response of CBMCs, total IgE and cross placental transfer of TB specific IgG. Therefore, further studies should be conducted to determine the effect of these factors on neonatal immune response to BCG vaccination.     

Immune Defense Mechanisms in Fish to Protozoan and Helminth Infections

Fish respond to parasite infections (and infestations) by theproduction of antigen specific IgM-like antibodies as well asby the elaboration of nonspecific soluble factors and phagocyticcells. Fish infected with the hemoflagellates Trypanosoma andCryptobia generally elicit antibody and complement dependentresponses. The levels of these responses vary depending on ambienttemperature fluctuations. Below 10–15°C there is analmost complete depression of immune responsiveness. The protozoanthat has received the greatest emphasis regarding studies ofimmunity is Ichthyophthinus multifihis. Both primary and secondaryantibody responses are produced in fish to this parasite. Cellularresponses are also produced against "Ich." These cells (nonspecificcytotoxic cells) may provide an important (but previously notdescribed) component of anti-parasite resistance. The second major group of parasites considered in this revieware categorized as helminths. Among these, the cestodes, trematodes(mono- and digenetic), and Acanthocephala have been studiedfor elicitation of immune responses in fishes. For virtuallyall organisms studied, the host response was mediated via antibodies(plus complement in most cases). Cellular responses (neitherantigen specific nor phagocytic activities) have not been shownto mediate any type of anti-helminth response in fishes.     

Isoflavones,Genistein and Daidzein,Regulate Mucosal Immune Response by Suppressing Dendritic Cell Function

Lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, has been shown to have a strong adjuvant effect towards inhaled antigens contributing to airway inflammation. Isoflavones are anti-inflammatory molecules present in abundant quantities in soybeans. We investigated the effect of isoflavones on human dendritic cell (DC) activation via LPS stimulation and subsequent DC-mediated effector cell function both in vitro and in a mouse model of upper airway inflammation. Human monocyte-derived DCs (MDDC) were matured with LPS (or TNF-α) +/− isoflavones (genistein or daidzein). The surface expression levels of DC activation markers were analyzed by flow cytometry. Mature DCs +/− isoflavones were washed and cultured with freshly-isolated allogenic naïve CD4⁺ T cells for 5 days or with autologous natural killer (NK) cells for 2 hours. The percentages of proliferating IFN-γ⁺ CD4⁺ T cells and cytokine levels in culture supernatants were assessed. NK cell degranulation and DC cytotoxicity were measured by flow cytometry. Isoflavones significantly suppressed the activation-induced expression of DC maturation markers (CD83, CD80, CD86) and MHC class I but not MHC class II molecules in vitro. Isoflavone treatment inhibited the ability of LPS-DCs to induce IFN-γ in CD4⁺ T cells. NK cell degranulation and the percentage of dead DCs were significantly increased in isoflavone-treated DC-NK co-culture experiments. Dietary isoflavones suppressed the mucosal immune response to intra-nasal sensitization of mice to ovalbumin. Similar results were obtained when isoflavones were co-administered during sensitization. These results demonstrate that soybean isoflavones suppress immune sensitization by suppressing DC-maturation and its subsequent DC-mediated effector cell functions.     

Specific Missense Alleles of the Arabidopsis Jasmonic Acid Co-Receptor COI1 Regulate Innate Immune Receptor Accumulation and Function

Plants utilize proteins containing nucleotide binding site (NB) and leucine-rich repeat (LRR) domains as intracellular innate immune receptors to recognize pathogens and initiate defense responses. Since mis-activation of defense responses can lead to tissue damage and even developmental arrest, proper regulation of NB–LRR protein signaling is critical. RAR1, SGT1, and HSP90 act as regulatory chaperones of pre-activation NB–LRR steady-state proteins. We extended our analysis of mutants derived from a rar1 suppressor screen and present two allelic rar1 suppressor (rsp) mutations of Arabidopsis COI1. Like all other coi1 mutations, coi1^rsp missense mutations impair Jasmonic Acid (JA) signaling resulting in JA–insensitivity. However, unlike previously identified coi1 alleles, both coi1^rsp alleles lack a male sterile phenotype. The coi1^rsp mutants express two sets of disease resistance phenotypes. The first, also observed in coi1-1 null allele, includes enhanced basal defense against the virulent bacterial pathogen Pto DC3000 and enhanced effector-triggered immunity (ETI) mediated by the NB–LRR RPM1 protein in both rar1 and wild-type backgrounds. These enhanced disease resistance phenotypes depend on the JA signaling function of COI1. Additionally, the coi1^rsp mutants showed a unique inability to properly regulate RPM1 accumulation and HR, exhibited increased RPM1 levels in rar1, and weakened RPM1-mediated HR in RAR1. Importantly, there was no change in the steady-state levels or HR function of RPM1 in coi1-1. These results suggest that the coi1^rsp proteins regulate NB–LRR protein accumulation independent of JA signaling. Based on the phenotypic similarities and genetic interactions among coi1^rsp, sgt1b, and hsp90.2^rsp mutants, our data suggest that COI1 affects NB–LRR accumulation via two NB–LRR co-chaperones, SGT1b and HSP90. Together, our data demonstrate a role for COI1 in disease resistance independent of JA signaling and provide a molecular link between the JA and NB–LRR signaling pathways.