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共278条结果
  • 1.

    【2hr】Protective immunity to liver-stage malaria

    包量

    机译 对肝期疟疾的保护性免疫
    摘要：Despite decades of research and recent clinical trials, an efficacious long-lasting preventative vaccine for malaria remains elusive. This parasite infects mammals via mosquito bites, progressing through several stages including the relatively short asymptomatic liver stage followed by the more persistent cyclic blood stage, the latter of which is responsible for all disease symptoms. As the liver acts as a bottleneck to blood-stage infection, it represents a potential site for parasite and disease control. In this review, we discuss immunity to liver-stage malaria. It is hoped that the knowledge gained from animal models of malaria immunity will translate into a more powerful and effective vaccine to reduce this global health problem.
  • 2.

    【2hr】Autoantibodies against CD80 in patients with COPD

    包量

    机译 COPD患者抗CD80的自身抗体
    摘要：Chronic obstructive pulmonary disease (COPD) is an inflammation disorder and possibly an autoimmune disease. The components of the autoimmune response in the circulatory system are of considerable interest to clinicians. Because aberrations of costimulation status have been noted in COPD, the presence of autoantibodies to B7 costimulatory factor CD80 were investigated in a cohort of patients. Recombinant rs1CD80 (lacking the transmembrane domain of CD80) was used for Western blot analysis and ELISA to investigate the presence of autoantibodies in sera of patients with stable COPD and in controls without COPD. Cytokines IL-6 and IL-8 were detected using ELISA. Western blot revealed a specific band reacting to rs1CD80 by diluting sera pool of patients, which indicated the existence of autoantibodies to CD80. The serum level of anti-rs1CD80 was higher in patients with COPD than in controls(P=0.0185) and was positively correlated to the serum level of IL-6 (r=0.797, P<0.001) and IL-8 (r=0.608, P<0.001). There was a tendency that more higher level of anti-rs1CD80, more severe COPD stage. The existence of autoantibodies to costimulatory factor CD80 may suggest a pathogenic role of costimulatory factors in COPD.
  • 3.

    【2hr】Hepatitis C virus drives the pathogenesis of hepatocellular carcinoma: from immune evasion to carcinogenesis

    包量

    机译 丙型肝炎病毒驱动肝细胞癌的发病机理：从免疫逃逸到癌变
    摘要：Persistent hepatitis C virus (HCV) infection is associated with high incidence of hepatocellular carcinoma (HCC), the most common primary malignancy of the liver with over half a million new cases diagnosed annually worldwide. The aryl hydrocarbon receptor (AhR) is a ubiquitously expressed transcription factor and its activation by environmental chemicals and by its endogenous ligand kynurenine (Kyn) has been implicated in a variety of tumour-promoting processes such as transformation, tumorigenesis and in immunosuppression that enables tumour survival and growth. Kyn is generated constitutively by human tumour cells via tryptophan (Trp)-2,3-dioxygenase (TDO), a Trp-degrading enzyme expressed in liver, brain and cancer cells. Notably, it has been shown that TDO-derived Kyn suppresses anti-tumour immune responses, thus promoting tumour-cell survival through activation of the AhR pathway. In the context of HCV infection-associated HCC, it was shown that AhR signalling is increased in HCV-infected hepatocytes, and that modifications in the expression of AhR pathway-specific genes are associated with the progression of HCV infection into HCC. Based on these observations, we present and discuss here the hypothesis that HCV infection promotes HCC by modulation of the TDO–Kyn–AhR pathway, resulting in tumorigenesis as well as in suppression of both anti-HCV and anti-tumour immune responses.
  • 4.

    【2hr】Expression profile of novel cell surface molecules on different subsets of human peripheral blood antigen-presenting cells

    包量

    机译 新型细胞表面分子在人外周血抗原呈递细胞不同亚群上的表达谱
    摘要：Although major steps have been recently made in understanding the role of the distinct subsets of dendritic cells (DC)/antigen-presenting cells (APC), further studies are required to unravel their precise role, including in-depth immunophenotypic characterisation of these cells. Here, we used eight-colour flow cytometry to investigate the reactivity of a panel of 72 monoclonal antibodies (including those clustered in seven new Cluster of Differentiation, CD) on different subsets of APC in peripheral blood (PB) samples from five healthy adults. These experiments were performed in the context of the Tenth International Workshop on Human Leukocyte Differentiation Antigens (HLDA10). Plasmacytoid DC was the only cell population that expressed CD85g and CD195, whereas they lacked all of the other molecules investigated. In contrast, myeloid DC mostly expressed inhibitory C-type lectin receptors (CLRs) and other inhibitory-associated molecules, whereas monocytes expressed both inhibitory and activating CLRs, together with other phagocytosis-associated receptors. Within monocytes, progressively lower levels of expression were generally observed from classical monocytes (cMo) to SLAN− and SLAN+ non-classical monocytes (ncMo) for most of the molecules expressed, except for the CD368 endocytic receptor. This molecule was found to be positive only in cMo, and the CD369 and CD371 modulating/signalling receptors. In addition, the CD101 inhibitory molecule was found to be expressed at higher levels in SLAN+ vs SLAN− ncMo. In summary, the pattern of expression of the different signalling molecules and receptors analysed in this work varies among the distinct subsets of PB APCs, with similar profiles for molecules within each functional group. These findings suggest unique pattern-recognition and signalling capabilities for distinct subpopulations of APCs, and therefore, diverse functional roles.
  • 5.

    【2hr】Role of human milk oligosaccharides in Group B Streptococcus colonisation

    包量

    机译 人乳寡糖在B组链球菌定植中的作用
    摘要：Group B Streptococcus (GBS) infection is a major cause of morbidity and mortality in infants. The major risk factor for GBS disease is maternal and subsequent infant colonisation. It is unknown whether human milk oligosaccharides (HMOs) protect against GBS colonisation. HMO production is genetically determined and linked to the Lewis antigen system. We aimed to investigate the association between HMOs and infant GBS colonisation between birth and postnatal day 90. Rectovaginal swabs were collected at delivery, as well as colostrum/breast milk, infant nasopharyngeal and rectal swabs at birth, 6 days and days 60–89 postpartum from 183 Gambian mother/infant pairs. GBS colonisation and serotypes were determined using culture and PCR. 1H nuclear magnetic resonance spectroscopy was used to characterise the mother's Lewis status and HMO profile in breast milk. Mothers who were Lewis-positive were significantly less likely to be colonised by GBS (X2=12.50, P<0.001). Infants of Lewis-positive mothers were less likely GBS colonised at birth (X2=4.88 P=0.03) and more likely to clear colonisation between birth and days 60–89 than infants born to Lewis-negative women (P=0.05). There was no association between Secretor status and GBS colonisation. In vitro work revealed that lacto-N-difucohexaose I (LNDFHI) correlated with a reduction in the growth of GBS. Our results suggest that HMO such as LNDFHI may be a useful adjunct in reducing maternal and infant colonisation and hence invasive GBS disease. Secretor status offers utility as a stratification variable in GBS clinical trials.
  • 6.

    【2hr】MAIT cells: new guardians of the liver

    包量

    机译 MAIT细胞：肝脏的新守护者
    摘要：The liver is an important immunological organ that remains sterile and tolerogenic in homeostasis, despite continual exposure to non-self food and microbial-derived products from the gut. However, where intestinal mucosal defenses are breached or in the presence of a systemic infection, the liver acts as a second 'firewall', because of its enrichment with innate effector cells able to rapidly respond to infections or tissue dysregulation. One of the largest populations of T cells within the human liver are mucosal-associated invariant T (MAIT) cells, a novel innate-like T-cell population that can recognize a highly conserved antigen derived from the microbial riboflavin synthesis pathway. MAIT cells are emerging as significant players in the human immune system, associated with an increasing number of clinical diseases of bacterial, viral, autoimmune and cancerous origin. As reviewed here, we are only beginning to investigate the potential role of this dominant T-cell subset in the liver, but the reactivity of MAIT cells to both inflammatory cytokines and riboflavin derivatives suggests that MAIT cells may have an important role in first line of defense as part of the liver firewall. As such, MAIT cells are promising targets for modulating the host defense and inflammation in both acute and chronic liver diseases.
  • 7.

    【2hr】CTI special feature on innate immune responses and vaccine design

    包量

    机译 CTI关于先天免疫反应和疫苗设计的特色
    摘要：
  • 8.

    【2hr】Prospective studies of infectious mononucleosis in university students

    包量

    机译 大学生传染性单核细胞增多症的前瞻性研究
    摘要：We performed an intensive prospective study designed to obtain as much data as possible on the incubation and early illness periods of primary Epstein–Barr virus (EBV) infection. Undergraduate students who lacked EBV antibody and oral EBV DNA (EBV-naive) were seen every 2 weeks during their freshman year. Clinical and behavioral data, oral washes and venous blood were obtained. EBV antibodies were quantified by enzyme immunoassay and viral loads by PCR. During a median 8 months of observation, 14/85 subjects experienced primary EBV infections (24 cases/100 person-years). The only significant risk factor for acquisition of EBV infection was deep kissing (P=0.02). Eleven subjects had infectious mononucleosis with a median duration of 21 days. Two subjects were hospitalized. Infections were initially identified in 12 subjects by finding EBV DNA in oral cells before onset of symptoms and in 2 subjects by symptom reporting. EBV DNA and viral capsid antigen (VCA) IgM and gp350 IgG antibodies were present in the blood before onset of illness. To provide a more robust evaluation of primary EBV infection in undergraduate university students, we combined data on risk factors and antibody responses from this and an earlier study that used the exact same clinical and laboratory methods. The observation that the only significant risk factor for acquisition of EBV infection was deep kissing was confirmed. Most importantly, higher amounts of gp350 antibody correlated significantly with a lower severity of infectious mononucleosis (P<0.0001), which strengthens the rationale for a gp350-based prophylactic EBV vaccine.
  • 9.

    【2hr】Conditions for the generation of cytotoxic CD4+ Th cells that enhance CD8+ CTL-mediated tumor regression

    包量

    机译 增强CD8 + CTL介导的肿瘤消退的细胞毒性CD4 + Th细胞生成的条件
    摘要：Adoptive cell therapies (ACTs) using tumor-reactive T cells have shown clinical benefit and potential for cancer treatment. While the majority of the current ACT are focused on using CD8+ cytotoxic T lymphocytes (CTL), others have shown that the presence of tumor-reactive CD4+ T helper (Th) cells can greatly enhance the anti-tumor activity of CD8+ CTL. However, difficulties in obtaining adequate numbers of CD4+ Th cells through in vitro expansion can limit the application of CD4 Th cells in ACT. This study aims to optimize the culture conditions for mouse CD4 T cells to provide basic information for animal studies of ACT using CD4 T cells. Taking advantage of the antigen-specificity of CD4+ Th cells from OT-II transgenic mice, we examined different methodologies for generating antigen-specific CD4+ Th1 cells in vitro. We found that cells grown in complete advanced-DMEM/F12 medium supplemented with low-dose IL-2 and IL-7 induced substantial cell expansion. These Th cells were Th1-like, as they expressed multiple Th1-cytokines and exhibited antigen-specific cytotoxicity. In addition co-transfer of these CD4+ Th1-like cells with CD8+ CTL significantly enhanced tumor regression, leading to complete cure in 80% of mice bearing established B16-OVA. These observations indicate that the CD4+ Th1-like cells generated using the method we optimized are functionally active to eliminate their target cells, and can also assist CD8+ CTL to enhance tumor regression. The findings of this study provide valuable data for further research into in vitro expansion of CD4+ Th1-like cells, with potential applications to cancer treatment involving ACT.
  • 10.

    【2hr】CTI special feature on inflammatory diseases: a translational perspective

    包量

    机译 CTI关于炎症性疾病的专题报道：翻译角度
    • 作者：Connie HY Wong
    • 刊名：Clinical Translational Immunology
    • 2016年第8期
    摘要：
  • 11.

    【2hr】Understanding natural herpes simplex virus immunity to inform next-generation vaccine design

    包量

    机译 了解天然单纯疱疹病毒免疫力为下一代疫苗设计提供信息
    摘要：Incremental advances in our knowledge of how natural immune control of herpes simplex virus (HSV) develops have yielded insight as to why previous vaccine attempts have only been partially successful, however, our understanding of these pathways, particularly in humans, is still incomplete. Further elucidation of the innate immune events that are responsible for stimulating these effector responses is required to accurately inform vaccine design. An enhanced understanding of the mechanism of action of novel adjuvants will also facilitate the rational choice of adjuvant to optimise such responses. Here we review the reasons for the hitherto partial HSV vaccine success and align these with our current knowledge of how natural HSV immunity develops. In particular, we focus on the innate immune response and the role of dendritic cells in inducing protective T-cell responses and how these pathways might be recapitulated in a vaccine setting.
  • 12.

    【2hr】Repertoire comparison of the B-cell receptor-encoding loci in humans and rhesus macaques by next-generation sequencing

    包量

    机译 下一代测序技术比较人和猕猴中B细胞受体的编码基因座
    摘要：Rhesus macaques (RMs) are a widely used model system for the study of vaccines, infectious diseases and microbial pathogenesis. Their value as a model lies in their close evolutionary relationship to humans, which, in theory, allows them to serve as a close approximation of the human immune system. However, despite their prominence as a human surrogate model system, many aspects of the RM immune system remain ill characterized. In particular, B cell-mediated immunity in macaques has not been sufficiently characterized, and the B-cell receptor-encoding loci have not been thoroughly annotated. To address these gaps, we analyzed the circulating heavy- and light-chain repertoires in humans and RMs by next-generation sequencing. By comparing V gene segment usage, J-segment usage and CDR3 lengths between the two species, we identified several important similarities and differences. These differences were especially notable in the IgM+ B-cell repertoire. However, the class-switched, antigen-educated B-cell populations converged on a set of similar characteristics, implying similarities in how each species responds to antigen. Our study provides the first comprehensive overview of the circulating repertoires of the heavy- and light-chain sequences in RMs, and provides insight into how they may perform as a model system for B cell-mediated immunity in humans.
  • 13.

    【2hr】Experimental design considerations in microbiota/inflammation studies

    包量

    机译 微生物/炎症研究中的实验设计注意事项
    摘要：There is now convincing evidence that many inflammatory diseases are precipitated, or at least exacerbated, by unfavourable interactions of the host with the resident microbiota. The role of gut microbiota in the genesis and progression of diseases such as inflammatory bowel disease, obesity, metabolic syndrome and diabetes have been studied both in human and in animal, mainly rodent, models of disease. The intrinsic variation in microbiota composition, both within one host over time and within a group of similarly treated hosts, presents particular challenges in experimental design. This review highlights factors that need to be taken into consideration when designing animal trials to investigate the gastrointestinal tract microbiota in the context of inflammation studies. These include the origin and history of the animals, the husbandry of the animals before and during experiments, details of sampling, sample processing, sequence data acquisition and bioinformatic analysis. Because of the intrinsic variability in microbiota composition, it is likely that the number of animals required to allow meaningful statistical comparisons across groups will be higher than researchers have generally used for purely immune-based analyses.
  • 14.

    【2hr】Elucidating novel disease mechanisms in severe asthma

    包量

    机译 阐明严重哮喘的新型疾病机制
    摘要：Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure. We have developed novel murine models of respiratory infection-induced, severe, steroid-resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. Hypothesis-driven studies can elucidate the roles of specific factors and pathways. Alternatively, 'Omics approaches can be used to rapidly generate new targets. Similar approaches can be used in other diseases.
  • 15.

    【2hr】The interplay between microbiota and inflammation: lessons from peritonitis and sepsis

    包量

    机译 微生物群与炎症之间的相互作用：腹膜炎和败血症的教训
    摘要：Mammals harbor a complex gut-associated microbiota, comprising bacteria that provide immunological, metabolic and neurological benefits to the host, and contribute to their well-being. However, dysregulation of the microbiota composition, known as dysbiosis, along with the associated mucosal immune response have a key role in the pathogenesis of many inflammatory diseases, including inflammatory bowel diseases (IBDs), type 1 and type 2 diabetes, asthma, multiple sclerosis, among others. In addition, outside the gut lumen, bacteria from microbiota are the causative agent of peritoneal inflammation, abdominal sepsis and systemic sepsis. Critical care interventions during sepsis by antibiotics induce dysbiosis and present acute and long-term poor prognosis. In this review, we discuss immunomodulatory effects of the microbial molecules and products, highlighting the role of Bacteroides fragilis, a human commensal with ambiguous interactions with the host. Moreover, we also address the impact of antibiotic treatment in sepsis outcome and discuss new insights for microbiota modulation.
  • 16.

    【2hr】Platelets and coagulation in infection

    包量

    机译 感染中的血小板和凝血
    摘要：Disseminated intravascular coagulation (DIC) is a frequent complication in sepsis that is associated with worse outcomes and higher mortality in patients. In addition to the uncontrolled generation of thrombi throughout the patient's vasculature, DIC often consumes large quantities of clotting factors leaving the patient susceptible to hemorrhaging. Owing to these complications, patients often receive anticoagulants to treat the uncontrolled clotting, often with mixed outcomes. This lack of success with the current array of anticoagulants can be partly explained by the fact that during sepsis clotting is often initiated by the immune system. Systemic inflammation has the capacity to activate and amplify coagulation and, as such, potential therapies for the treatment of sepsis-associated DIC need to address the interaction between inflammation and coagulation. Recent studies have suggested that platelets and neutrophil extracellular traps (NETs) are the key mediators of infection-induced coagulation. This review explores current anticoagulant therapies and discusses the development of future therapies to target platelet and NET-mediated coagulation.
  • 17.

    【2hr】Characterizing the inflammatory response in esophageal mucosal biopsies in children with eosinophilic esophagitis

    包量

    机译 嗜酸性粒细胞性食管炎患儿食管黏膜活检中炎症反应的特征
    摘要：Eosinophilic esophagitis (EoE) is an emerging allergic, IgE- and non-IgE (Th2 cell)-mediated disease. There are major gaps in the understanding of the basic mechanisms that drive the persistence of EoE. We investigated whether esophageal biopsies from children with EoE demonstrate an inflammatory response that is distinct from normal controls. We prospectively enrolled 84 patients, of whom 77 were included in our analysis, aged 4–17 years (12.8±3.8 years; 81% males). Five esophageal biopsies were collected from each patient at the time of endoscopy. Intramucosal lymphocytes were isolated, phenotyped and stimulated with phorbol 12-myristate 13-acetate/ionomycin to measure their potential to produce cytokines via flow cytometry. We also performed cytokine arrays on 72-h biopsy culture supernatants. CD8+ T cells, compared with CD4+ T cells, synthesized more TNF-α and interferon (IFN)-γ after mitogen stimulation in the EoE-New/Active vs EoE-Remission group (P=0.0098; P=0.02) and controls (P=0.0008; P=0.03). Culture supernatants taken from explant esophageal tissue contained 13 analytes that distinguished EoE-New/Active from EoE-Remission and Controls. Principal component analysis and cluster analysis based on these analytes distinctly separated EoE-New/Active from EoE-Remission and Controls. In summary, we have identified a previously unappreciated role for CD8+ T lymphocytes with potential to produce TNF-α and IFN-γ in EoE. Our results suggest that CD8+ T cells have a role in the persistence or progression of EoE. We have also identified a panel of analytes produced by intact esophageal biopsies that differentiates EoE-New/Active from EoE-Remission and controls. Our results suggest that esophageal epithelial cells may have specific immune effector functions in EoE that control the type and amplitude of inflammation.
  • 18.

    【2hr】New insights into therapeutic strategies for gut microbiota modulation in inflammatory diseases

    包量

    机译 炎症疾病中肠道微生物群调节治疗策略的新见解
    摘要：The interaction between the gut microbiota and the host immune system is very important for balancing and resolving inflammation. The human microbiota begins to form during childbirth; the complex interaction between bacteria and host cells becomes critical for the formation of a healthy or a disease-promoting microbiota. C-section delivery, formula feeding, a high-sugar diet, a high-fat diet and excess hygiene negatively affect the health of the microbiota. Considering that the majority of the global population has experienced at least one of these factors that can lead to inflammatory disease, it is important to understand strategies to modulate the gut microbiota. In this review, we will discuss new insights into gut microbiota modulation as potential strategies to prevent and treat inflammatory diseases. Owing to the great advances in tools for microbial analysis, therapeutic strategies such as prebiotic, probiotic and postbiotic treatment and fecal microbiota transplantation have gained popularity.
  • 19.

    【2hr】The microbiota and chronic kidney diseases: a double-edged sword

    包量

    机译 微生物群和慢性肾脏疾病：一把双刃剑
    摘要：Recent findings regarding the influence of the microbiota in many inflammatory processes have provided a new way to treat diseases. Now, one may hypothesize that the origin of a plethora of diseases is related to the health of the gut microbiota and its delicate, although complex, interface with the epithelial and immune systems. The ‘westernization' of diets, for example, is associated with alterations in the gut microbiota. Such alterations have been found to correlate directly with the increased incidence of diabetes and hypertension, the main causes of chronic kidney diseases (CKDs), which, in turn, have a high estimated prevalence. Indeed, data have arisen showing that the progression of kidney diseases is strictly related to the composition of the microbiota. Alterations in the gut microbiota diversity during CKDs do not only have the potential to exacerbate renal injury but may also contribute to the development of associated comorbidities, such as cardiovascular diseases and insulin resistance. In this review, we discuss how dysbiosis through alterations in the gut barrier and the consequent activation of immune system could intensify the progression of CKD and vice versa, how CKDs can modify the gut microbiota diversity and abundance.
  • 20.

    【2hr】Is the risk of cardiovascular disease altered with anti-inflammatory therapies? Insights from rheumatoid arthritis

    包量

    机译 抗炎疗法会改变心血管疾病的风险吗？类风湿关节炎的见解
    摘要：Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Atherosclerosis is the most common form of CVD, which is complex and multifactorial with an elevated risk observed in people with either metabolic or inflammatory diseases. Accumulating evidence now links obesity with a state of chronic low-grade inflammation and has renewed our understanding of this condition and its associated comorbidities. An emerging theme linking disease states with atherosclerosis is the increased production of myeloid cells, which can initiate and exacerbate atherogenesis. Although anti-inflammatory drug treatments exist and have been successfully used to treat inflammatory conditions such as rheumatoid arthritis (RA), a commonly observed side effect is dyslipidemia, inadvertently, a major risk factor for the development of atherosclerosis. The mechanisms leading to dyslipidemia associated with anti-inflammatory drug use and whether CVD risk is actually increased by this dyslipidemia are of great therapeutic importance and currently remain poorly understood. Here we review recent data providing links between inflammation, hematopoiesis, dyslipidemia and CVD risk in the context of anti-inflammatory drug use.
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