secretory immunoglobulin A

分泌性免疫球蛋白 A
  • 文章类型: Journal Article
    在胃肠粘膜,分泌性免疫球蛋白A(SIgA)与微生物群的组成之间有着密切的合作,其目的是维持体内平衡并充当保护屏障。本研究的目的是确定消化道不同部位(小肠,盲肠,结肠和直肠)九匹健康的马及其在粪便中的反射。为此,我们确定:微生物组的组成(通过16SrRNA基因分析的高变区V3-V4和V7-V9的下一代测序),肠内容物样品中SIgA的量(通过ELISA),以及组织样本中产生IgA的细胞(IgA)的数量(通过免疫组织化学分析)。小肠和大结肠在微生物组的组成和多样性方面存在显著差异,以及粘膜固有层中IgA细胞的数量和肠腔中SIgA的丰度。与大肠相关的小肠的特征是IgA+细胞较少,肠道内容物中更多的SIgA和较少多样化的微生物组。然而,盲肠似乎是第三个独立的生态系统,具有大量的IgA+细胞和多样化的微生物组。粪便样本反映了大结肠的当前状态,就微生物组和SIgA含量而言;然而,目前尚不清楚它可能在多大程度上受到消化道其他部位菌群失调的影响。
    In the gastrointestinal mucosa, there is a close cooperation between secretory immunoglobulin A (SIgA) and the composition of the microbiota, which aims to maintain homeostasis as well as act as a protective barrier. The purpose of this study was to determine the composition of microbiota and SIgA production in different parts of the digestive tract (small intestine, cecum, colon and rectum) of nine healthy horses and its reflection in the feces. For this purpose, we determined: the composition of the microbiome (by next-generation Sequencing of Hypervariable Regions V3-V4 and V7-V9 of the 16 S rRNA gene analysis), the amount of SIgA in the intestinal content samples (by ELISA), as well as the number of IgA-producing cells (IgA+) in the tissue samples (by immohistochemical analysis). Significant differences were observed between the small intestine and the large colon in the composition and diversity of the microbiome, as well as the number of IgA + cells in the mucosal lamina propria and the abundance of SIgA in the intestinal lumen. The small intestine in relation to the large colon is characterised by fewer IgA + cells, more SIgA in the intestinal contents and a less diverse microbiome. However, the cecum appears to be the third separate ecosystem, with a high number of IgA + cells and a diverse microbiome. The fecal sample reflects the current state of the large colon, both in terms of the microbiome and SIgA content; however, it is not known to what extent it may be influenced by dysbiosis in other parts of the digestive tract.
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  • 文章类型: Journal Article
    电子烟(vapes)被积极使用,它们的使用在全球范围内增长,尤其是年轻人。由于存在未经证实的谣言,它用于治疗吸烟成瘾,因为它有助于戒烟,因此传播迅速。然而,E.C通过影响口腔微生物组和唾液成分对牙齿健康具有负面影响。这项研究的目的是评估电子烟对龋齿的影响,与电子烟使用者唾液中的葡萄糖基转移酶B和分泌性免疫球蛋白有关。将90名活跃男性分为两组:45名电子烟吸烟者以及45名非电子烟吸烟者作为对照组。对研究组进行了口腔检查,并记录了腐烂的缺失填充牙齿表面(DMFS)。此外,使用夹心酶联免疫吸附试验(ELISA)收集未刺激的唾液以评估唾液葡萄糖基转移酶B和分泌性免疫球蛋白A。获得的结果表明,腐烂,失踪,和填充曲面值(DMFS),唾液葡萄糖基转移酶B,与对照组相比,研究组的唾液分泌免疫球蛋白A增加。此外,葡萄糖基转移酶B之间的相关性,分泌性免疫球蛋白A,DMFS呈阳性且显著。结论电子烟可能对唾液成分和龋齿有影响。
    Electronic cigarettes (vapes) are actively used, and their use is growing globally, especially among young people. Its spread is rapid due to the presence of unproven rumors that it is used to treat smoking addiction as it aids in smoking cessation. However, E.C has a negative impact on dental health by affecting the oral microbiome and salivary components. The goal of this study was to evaluate the impact of electronic cigarettes on dental caries in relation to glucosyltransferase B and secretory immunoglobulin in the saliva of electronic cigarette users. Ninety active males were divided into two groups: 45 electronic-cigarette smokers in addition to 45 non-electronic-cigarette smokers as a control group. An oral examination was performed on the studied groups, and decayed missing filling tooth surfaces (DMFS) were documented. Additionally, unstimulated saliva was collected to evaluate salivary glucosyltransferase B and secretory immunoglobulin A by using a sandwich enzyme-linked immune-sorbent assay (ELISA). The obtained outcomes showed that decayed, missing, and filled Surfaces values(DMFS), salivary glucosyltransferase B, and salivary secretory immunoglobulin A were greater in the study group than in control group. Additionally, a correlation between glucosyltransferase B, secretory immunoglobulin A, and DMFS was positive and significant. It was concluded that e-cigarettes may have an effect on saliva components and dental caries.
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  • 文章类型: Journal Article
    分泌型IgA(SIgA)为粘膜免疫治疗提供了一个有希望的途径,但在表达方面面临挑战,净化,和稳定性。IgA存在于两种主要同种型中,IgA1和IgA2,其中IgA2进一步细分为两种常见的同种异型:IgA2m(1)和IgA2m(2)。IgA1和IgA2之间的主要差异位于铰链区,IgA1具有13个氨基酸的延伸,包括多达六个O-糖基化位点。此外,IgA2m(1)同种异型在重链和轻链之间缺乏共价二硫键,它存在于IgA1和IgA2m(2)中。虽然IgA1表现出优越的表位结合和病原体中和,IgA2表现出增强的效应子功能和抗粘膜细菌降解的稳定性。然而,IgA2m(1)同种异型中的非共价键增加了生产和稳定性的挑战。引入不同的单突变旨在促进交替的二硫键形成以减轻这些挑战。我们将四种不同的IgA2版本与IgA1进行比较,以进一步开发针对SARS-CoV-2的分泌性IgA抗体,用于局部递送至粘膜表面。我们的结果表明,SIgA2(P221R)在烟草中的表达水平和组装功效显着提高。此外,工程SigA2在生理和酸性条件下显示出更高的热稳定性,并且可以使用网状雾化器进行雾化。总之,我们的研究阐明了稳定性增强突变在克服与SIgA表达和稳定性相关的障碍方面的益处.
    Secretory IgA (SIgA) presents a promising avenue for mucosal immunotherapy yet faces challenges in expression, purification, and stability. IgA exists in two primary isotypes, IgA1 and IgA2, with IgA2 further subdivided into two common allotypes: IgA2m(1) and IgA2m(2). The major differences between IgA1 and IgA2 are located in the hinge region, with IgA1 featuring a 13-amino acid elongation that includes up to six O-glycosylation sites. Furthermore, the IgA2m(1) allotype lacks a covalent disulfide bond between heavy and light chains, which is present in IgA1 and IgA2m(2). While IgA1 demonstrates superior epitope binding and pathogen neutralization, IgA2 exhibits enhanced effector functions and stability against mucosal bacterial degradation. However, the noncovalent linkage in the IgA2m(1) allotype raises production and stability challenges. The introduction of distinct single mutations aims to facilitate an alternate disulfide bond formation to mitigate these challenges. We compare four different IgA2 versions with IgA1 to further develop secretory IgA antibodies against SARS-CoV-2 for topical delivery to mucosal surfaces. Our results indicate significantly improved expression levels and assembly efficacy of SIgA2 (P221R) in Nicotiana benthamiana. Moreover, engineered SIgA2 displays heightened thermal stability under physiological as well as acidic conditions and can be aerosolized using a mesh nebulizer. In summary, our study elucidates the benefits of stability-enhancing mutations in overcoming hurdles associated with SIgA expression and stability.
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  • 文章类型: Journal Article
    人乳(HM)含有新生儿正常生长和发育所必需的必需常量营养素和生物活性化合物。人乳库收集的牛奶经过冷冻和巴氏灭菌后储存,降低其营养和生物价值。这项研究的目的是确定在零度以下温度(HS-ST)下高压储存对HM中大量营养素和生物活性蛋白的影响。作为对照样品,HM在0.1MPa下在相同温度下储存。使用MirisHM分析仪测定大量营养素和能量值。乳铁蛋白(LF),溶菌酶(LYZ)和α-乳白蛋白(α-LAC)含量采用高效液相色谱法检测,用ELISA试验定量分泌型免疫球蛋白A(sIgA)。结果表明,在60MPa/-5°C下储存90天后,大量营养素含量没有显着变化,78MPa/-7°C,111MPa/-10℃或130MPa/-12℃保留率高于LYZ的90%,α-LAC,在高达111MPa/-10°C的条件下储存的HM中观察到LF和sIgA。然而,在130MPa/-12°C时,LYZ和LF减少了,39%和89%,分别。HM在0.1MPa的零度以下温度下的储存不会影响碳水化合物或粗蛋白和真蛋白的含量。对于脂肪和能量值,在-5°C下储存90天后观察到显著降低。
    Human milk (HM) contains the essential macronutrients and bioactive compounds necessary for the normal growth and development of newborns. The milk collected by human milk banks is stored frozen and pasteurized, reducing its nutritional and biological value. The purpose of this study was to determine the effect of hyperbaric storage at subzero temperatures (HS-ST) on the macronutrients and bioactive proteins in HM. As control samples, HM was stored at the same temperatures under 0.1 MPa. A Miris HM analyzer was used to determine the macronutrients and the energy value. The lactoferrin (LF), lysozyme (LYZ) and α-lactalbumin (α-LAC) content was checked using high-performance liquid chromatography, and an ELISA test was used to quantify secretory immunoglobulin A (sIgA). The results showed that the macronutrient content did not change significantly after 90 days of storage at 60 MPa/-5 °C, 78 MPa/-7 °C, 111 MPa/-10 °C or 130 MPa/-12 °C. Retention higher than 90% of LYZ, α-LAC, LF and sIgA was observed in the HM stored at conditions of up to 111 MPa/-10 °C. However, at 130 MPa/-12 °C, there was a reduction in LYZ and LF, by 39 and 89%, respectively. The storage of HM at subzero temperatures at 0.1 MPa did not affect the content of carbohydrates or crude and true protein. For fat and the energy value, significant decreases were observed at -5 °C after 90 days of storage.
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  • 文章类型: Journal Article
    白色念珠菌,最常见的条件病原真菌之一,会导致局部表面感染和致命的全身感染,尤其是在免疫功能低下的人群中。分泌型免疫球蛋白A(sIgA)是调节白色念珠菌致病性的重要免疫蛋白。然而,sIgA对白色念珠菌的直接作用和机制尚不清楚。这里,我们研究了sIgA对白色念珠菌菌丝生长和口腔上皮细胞的毒力。我们的结果表明,sIgA显著抑制白色念珠菌菌丝生长,附着力,与IgG相比,对口腔上皮细胞的损害。根据转录组和RT-PCR分析,sIgA显著影响麦角甾醇生物合成途径。此外,sIgA显著降低麦角固醇水平,而添加外源麦角甾醇恢复白色念珠菌菌丝生长和粘附口腔上皮细胞,表明sIgA通过降低其麦角固醇水平抑制菌丝的生长和白色念珠菌的致病性。通过采用关键基因突变体(erg11Δ/Δ,3Δ/Δ,和erg3Δ/Δerg11Δ/Δ)来自麦角甾醇途径,sIgA失去了对这些突变体的菌丝抑制,而sIgA也降低了erg11Δ/Δ和erg3Δ/Δ的抑制作用,并失去了erg3Δ/Δerg11Δ/Δ对口腔上皮细胞粘附的抑制作用,进一步证明了通过麦角固醇途径对sIgA的菌丝抑制。我们首次证明sIgA通过影响麦角甾醇生物合成抑制白色念珠菌菌丝发育和毒力,并表明麦角甾醇是白色念珠菌-宿主细胞相互作用的关键调节因子。关键点:•sIgA抑制白色念珠菌菌丝生长•sIgA抑制白色念珠菌对宿主细胞的毒力•sIgA通过降低其麦角固醇水平影响白色念珠菌菌丝和毒力。
    Candida albicans, one of the most prevalent conditional pathogenic fungi, can cause local superficial infections and lethal systemic infections, especially in the immunocompromised population. Secretory immunoglobulin A (sIgA) is an important immune protein regulating the pathogenicity of C. albicans. However, the actions and mechanisms that sIgA exerts directly against C. albicans are still unclear. Here, we investigated that sIgA directs against C. albicans hyphal growth and virulence to oral epithelial cells. Our results indicated that sIgA significantly inhibited C. albicans hyphal growth, adhesion, and damage to oral epithelial cells compared with IgG. According to the transcriptome and RT-PCR analysis, sIgA significantly affected the ergosterol biosynthesis pathway. Furthermore, sIgA significantly reduced the ergosterol levels, while the addition of exogenous ergosterol restored C. albicans hyphal growth and adhesion to oral epithelial cells, indicating that sIgA suppressed the growth of hyphae and the pathogenicity of C. albicans by reducing its ergosterol levels. By employing the key genes mutants (erg11Δ/Δ, erg3Δ/Δ, and erg3Δ/Δ erg11Δ/Δ) from the ergosterol pathway, sIgA lost the hyphal inhibition on these mutants, while sIgA also reduced the inhibitory effects of erg11Δ/Δ and erg3Δ/Δ and lost the inhibition of erg3Δ/Δ erg11Δ/Δ on the adhesion to oral epithelial cells, further proving the hyphal repression of sIgA through the ergosterol pathway. We demonstrated for the first time that sIgA inhibited C. albicans hyphal development and virulence by affecting ergosterol biosynthesis and suggest that ergosterol is a crucial regulator of C. albicans-host cell interactions. KEY POINTS: • sIgA repressed C. albicans hyphal growth • sIgA inhibited C. albicans virulence to host cells • sIgA affected C. albicans hyphae and virulence by reducing its ergosterol levels.
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  • 文章类型: Journal Article
    免疫球蛋白A(IgA)是维持粘膜表面稳态的重要因素,然而管腔IgA水平差异很大。总IgA水平被认为是由对特定微生物的个体免疫应答驱动的。这里,我们发现益生元,果胶寡糖(pec-oligo),以T细胞依赖性方式在小肠中诱导高IgA水平。令人惊讶的是,停止pec-oligo治疗后保留了这种高IgA表型,在没有pec-oligo的情况下,水平或垂直的微生物组传播足以保持高IgA水平。有趣的是,在整个pec-oligo细菌群落中富集的细菌分类群与同一群落中IgA包被的微生物不同。相反,一组耐乙醇的微生物,高度富集的鼠尾草科细菌A2,驱动了IgA高表型。这些发现支持肠道适应性免疫模型,其中有限数量的微生物可以促进针对许多共生体的IgA的持久变化。
    Immunoglobulin A (IgA) is an important factor in maintaining homeostasis at mucosal surfaces, yet luminal IgA levels vary widely. Total IgA levels are thought to be driven by individual immune responses to specific microbes. Here, we found that the prebiotic, pectin oligosaccharide (pec-oligo), induced high IgA levels in the small intestine in a T cell-dependent manner. Surprisingly, this IgA-high phenotype was retained after cessation of pec-oligo treatment, and microbiome transmission either horizontally or vertically was sufficient to retain high IgA levels in the absence of pec-oligo. Interestingly, the bacterial taxa enriched in the overall pec-oligo bacterial community differed from IgA-coated microbes in this same community. Rather, a group of ethanol-resistant microbes, highly enriched for Lachnospiraceae bacterium A2, drove the IgA-high phenotype. These findings support a model of intestinal adaptive immunity in which a limited number of microbes can promote durable changes in IgA directed to many symbionts.
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  • 文章类型: Journal Article
    分泌型免疫球蛋白A(SIgA)是黏膜中最丰富的免疫球蛋白亚型之一。在抵御入侵病原体和抗原的一线保护中起着不可或缺的作用。因此,呼吸道SIgA在呼吸道黏膜免疫疾病中的作用越来越受到重视。虽然SIgA在肠黏膜免疫中的作用已被广泛研究,SIgA的细胞类型和细胞间的相互作用尚不清楚.这里,我们进行了广泛的相关研究,整理了SIgA与一些肺部疾病(COPD,哮喘,结核病,特发性肺纤维化,COVID-19,肺癌),发现SIgA参与各种肺部疾病的发病机制和进展,旨在为预防提供新的思路,诊断,以及相关肺部疾病的治疗。
    Secretory immunoglobulin A (SIgA) is one of the most abundant immunoglobulin subtypes among mucosa, which plays an indispensable role in the first-line protection against invading pathogens and antigens. Therefore, the role of respiratory SIgA in respiratory mucosal immune diseases has attracted more and more attention. Although the role of SIgA in intestinal mucosal immunity has been widely studied, the cell types responsible for SIgA and the interactions between cells are still unclear. Here, we conducted a wide search of relevant studies and sorted out the relationship between SIgA and some pulmonary diseases (COPD, asthma, tuberculosis, idiopathic pulmonary fibrosis, COVID-19, lung cancer), which found SIgA is involved in the pathogenesis and progression of various lung diseases, intending to provide new ideas for the prevention, diagnosis, and treatment of related lung diseases.
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  • 文章类型: Journal Article
    先前的工作表明,与肠道微生物群结合的分泌型IgA(SIgA)是可变的,可以调节宿主的炎症性肠反应。然而,SIgA功能结合微生物群的影响在早产儿中仍然未知,早产儿的不成熟上皮屏障使他们特别容易受到炎症的影响.这里,我们调查了SIgA与不同肠道通透性水平的妊娠<33周早产儿粪便中分离出的肠道微生物群的结合。我们发现SIgA与肠道微生物群结合可减弱早产儿的炎症反应。我们还观察到SIgA对微生物群的亲和力与婴儿肠屏障成熟之间存在显著的相关性。尽管如此,SIgA亲和力与发展宿主防御无关,例如粘液和炎性钙卫蛋白的产生,但它依赖于肠道屏障成熟时微生物群的变化。总之,我们报道了SIgA与微生物群的功能性结合与早产儿肠屏障的成熟度之间的关联,表明SIgA涂层的模式随着肠屏障的成熟而改变。
    Previous work has shown that Secretory-IgA (SIgA) binding to the intestinal microbiota is variable and may regulate host inflammatory bowel responses. Nevertheless, the impact of the SIgA functional binding to the microbiota remains largely unknown in preterm infants whose immature epithelial barriers make them particularly susceptible to inflammation. Here, we investigated SIgA binding to intestinal microbiota isolated from stools of preterm infants <33 weeks gestation with various levels of intestinal permeability. We found that SIgA binding to intestinal microbiota attenuates inflammatory reactions in preterm infants. We also observed a significant correlation between SIgA affinity to the microbiota and the infant\'s intestinal barrier maturation. Still, SIgA affinity was not associated with developing host defenses, such as the production of mucus and inflammatory calprotectin protein, but it depended on the microbiota shifts as the intestinal barrier matures. In conclusion, we reported an association between the SIgA functional binding to the microbiota and the maturity of the preterm infant\'s intestinal barrier, indicating that the pattern of SIgA coating is altered as the intestinal barrier matures.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    虽然近年来越来越多的证据表明花青素在治疗微生物群相关疾病方面具有益生特性,花青素摄取之间复杂的相互作用,肠道微生物群,和肠道粘膜免疫系统仍然知之甚少。这里,我们研究了越橘花色苷对肠道菌群组成和代谢的影响,和小鼠的肠道粘膜免疫系统。我们观察到肠系膜淋巴结(MLN)中产生IgA的浆细胞比例增加,小肠中分泌性免疫球蛋白A(sIgA)和抗菌肽的分泌增加。小肠转录组分析进一步表明花色苷影响IgA的产生。我们发现口服花青素通过维持厌氧肠道环境改变了肠道微生物群,促进sIgA和抗菌肽的分泌,下调共生细菌的细胞运动和移动遗传元件。这些观察结果表明,口服花色苷有助于维持肠道稳态,因此它可能在免疫疗法和相关领域中找到应用。
    While recent years have witnessed ever-growing evidence on the prebiotic attributes of anthocyanins for treatment of microbiota-associated diseases, the complex interplay between anthocyanin uptake, the gut microbiota, and the intestinal mucosal immune system remains poorly understood. Here, we investigate the effects of bilberry anthocyanins on the gut microbiota composition and metabolism, and the intestinal mucosal immune system of mice. We observed an increased proportion of IgA-producing plasma cells in the mesenteric lymph nodes (MLNs) and an enhanced secretion of secretory immunoglobulin A (sIgA) and antimicrobial peptides in the small intestine. Small intestine transcriptome analysis further suggested that anthocyanins influenced IgA production. We found that oral administration of anthocyanins altered the gut microbiota through maintaining the anaerobic intestinal environment, promoting the secretion of sIgA and antimicrobial peptides, and downregulating cell motility and mobile genetic elements of commensal bacteria. These observations suggest that the oral administration of anthocyanins helps in maintaining intestinal homeostasis and thus it may find applications in immunotherapy and related fields.
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