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Toll-like receptors in innate immunity and infectious diseases

Min-Hao WU, Ping ZHANG, Xi HUANG,

《医学前沿（英文）》 2010年第4卷第4期页码 385-393 doi: 10.1007/s11684-010-0600-x

摘要： The protective ability of host defense system is largely dependent on germ-line encoded pattern-recognition receptors (PRRs). These PRRs respond to a variety of exogenous pathogens or endogenous danger signals, by recognizing some highly conserved structures such as pathogen-associated molecular patterns (PAMPs) and danger/damage associated molecular patterns (DAMPs). The most studied PRRs are Toll-like receptors (TLRs). Activation of TLRs triggers production of inflammatory cytokines and type I interferons (IFNs) via myeloid differentiation primary response gene 88 (MyD88)-dependent or-independent signaling respectively, thereby modulating innate and adaptive immunity, as well as inflammatory responses. This review introduces the classification, structure, and specific ligands of TLRs, and focuses on their signal pathways and biological activities, as well as clinical relevance. These studies of TLRs in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases, including tuberculosis (TB), microbial keratitis, and hepatitis B and C.

关键词： Toll-like receptors innate immunity infectious disease inflammation

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Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

《农业科学与工程前沿（英文）》 2017年第4卷第3期页码 260-267 doi: 10.15302/J-FASE-2016116

摘要： The innate immune response is the first line of defense against viral invasion and pro-inflammatory chemokines and cytokines have a critical function in the innate immune responses against virus infections. The ability of a rabies virus (RABV) to induce the expression of chemokines and cytokines can lead to viral clearance from the central nervous system (CNS), whereas the ability to evade such expression and activation contributes to virulence and pathogenicity. In this review, the crucial contribution of chemokines/cytokines to clearing RABV from the CNS is discussed, including recruiting leukocytes into the CNS, enhancement of blood brain barrier permeability and activation of various immune cells that are essential for viral clearance. In addition, recombinant RABV expressing cytokines and chemokines can induce elevated innate and adaptive immune responses which result in clearing an established wild-type RABV infection in the CNS.

关键词： antiviral blood brain barrier chemokines and cytokines innate immunity rabies virus

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Autoimmunity in acute ischemic stroke and the role of blood—brain barrier: the dark side or the light one?

Nikolay V. Tsygan, Alexandr P. Trashkov, Igor V. Litvinenko, Viktoriya A. Yakovleva, Alexandr V. Ryabtsev, Andrey G. Vasiliev, Leonid P. Churilov

《医学前沿（英文）》 2019年第13卷第4期页码 420-426 doi: 10.1007/s11684-019-0688-6

摘要： This article presents a synopsis of the current data on the mechanisms of blood—brain barrier (BBB) alteration and autoimmune response in acute ischemic stroke. Most researchers confirm the relationship between the severity of immunobiochemical changes and clinical outcome of acute ischemic stroke. Ischemic stroke is accompanied by aseptic inflammation, which alters the brain tissue and exposes the co-stimulatory molecules of the immune system and the neuronal antigens. To date, BBB is not considered the border between the immune system and central nervous system, and the local immune subsystems are found within and behind the BBB. BBB disruption contributes to the leakage of brain autoantigens and induction of secondary autoimmune response to neuronal antigens and long-term inflammation. Glymphatic system function is altered and jeopardized both in hemorrhagic and ischemic stroke types. The receptors of innate immunity (toll-like receptor-2 and toll-like receptor-4) are also involved in acute ischemia—reperfusion injury. Immune response is related to the key processes of blood clotting and fibrinolysis. At the same time, the stroke-induced immune activation may promote reparation phenomena in the brain. Subsequent research on the reduction of the acute ischemic brain injury through the target regulation of the immune response is promising.

关键词： stroke blood–brain barrier autoimmunity innate immunity inflammation cell death

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Innate immune responses in RNA viral infection

Qian Xu, Yuting Tang, Gang Huang

《医学前沿（英文）》 2021年第15卷第3期页码 333-346 doi: 10.1007/s11684-020-0776-7

摘要： RNA viruses cause a multitude of human diseases, including several pandemic events in the past century. Upon viral invasion, the innate immune system responds rapidly and plays a key role in activating the adaptive immune system. In the innate immune system, the interactions between pathogen-associated molecular patterns and host pattern recognition receptors activate multiple signaling pathways in immune cells and induce the production of pro-inflammatory cytokines and interferons to elicit antiviral responses. Macrophages, dendritic cells, and natural killer cells are the principal innate immune components that exert antiviral activities. In this review, the current understanding of innate immunity contributing to the restriction of RNA viral infections was briefly summarized. Besides the main role of immune cells in combating viral infection, the intercellular transfer of pathogen and host-derived materials and their epigenetic and metabolic interactions associated with innate immunity was discussed. This knowledge provides an enhanced understanding of the innate immune response to RNA viral infections in general and aids in the preparation for the existing and next emerging viral infections.

关键词： innate immune viral infection intercellular signaling metabolic changes epigenetic changes

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Regulation of T cell immunity by cellular metabolism

null

《医学前沿（英文）》 2018年第12卷第4期页码 463-472 doi: 10.1007/s11684-018-0668-2

摘要：

T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate T cell immune responses, and alterations in T cell metabolism may result in many immunological disorders. In this review, we will summarize the main T cell metabolic pathways and the important factors participating in T cell metabolic programming during T cell homeostasis, differentiation, and function.

关键词： T cell immunity metabolic pathways nutrient uptake metabolic checkpoints

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Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

《医学前沿（英文）》 2022年第16卷第4期页码 596-609 doi: 10.1007/s11684-021-0868-z

摘要： Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.

关键词： innate immune checkpoint Siglec10 kidney renal clear cell carcinoma

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Innate and adaptive T cells in influenza disease

null

《医学前沿（英文）》 2018年第12卷第1期页码 34-47 doi: 10.1007/s11684-017-0606-8

摘要：

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, gd T cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and gd T cells as well as adaptive CD8⁺ and CD4⁺ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

关键词： influenza innate T cells CD4⁺ and CD8⁺ T cells vaccination

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Metabolism and immunity in breast cancer

Deyu Zhang, Xiaojie Xu, Qinong Ye

《医学前沿（英文）》 2021年第15卷第2期页码 178-207 doi: 10.1007/s11684-020-0793-6

摘要： Breast cancer is one of the most common malignancies that seriously threaten women’s health. In the process of the malignant transformation of breast cancer, metabolic reprogramming and immune evasion represent the two main fascinating characteristics of cancer and facilitate cancer cell proliferation. Breast cancer cells generate energy through increased glucose metabolism. Lipid metabolism contributes to biological signal pathways and forms cell membranes except energy generation. Amino acids act as basic protein units and metabolic regulators in supporting cell growth. For tumor-associated immunity, poor immunogenicity and heightened immunosuppression cause breast cancer cells to evade the host’s immune system. For the past few years, the complex mechanisms of metabolic reprogramming and immune evasion are deeply investigated, and the genes involved in these processes are used as clinical therapeutic targets for breast cancer. Here, we review the recent findings related to abnormal metabolism and immune characteristics, regulatory mechanisms, their links, and relevant therapeutic strategies.

关键词： breast cancer metabolism immunity cancer stem cells

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Rhizosphere immunity: targeting the underground for sustainable plant health management

Zhong WEI, Ville-Petri FRIMAN, Thomas POMMIER, Stefan GEISEN, Alexandre JOUSSET, Qirong SHEN

《农业科学与工程前沿（英文）》 2020年第7卷第3期页码 317-328 doi: 10.15302/J-FASE-2020346

摘要：

Managing plant health is a great challenge for modern food production and is further complicated by the lack of common ground between the many disciplines involved in disease control. Here we present the concept of rhizosphere immunity, in which plant health is considered as an ecosystem level property emerging from networks of interactions between plants, microbiota and the surrounding soil matrix. These interactions can potentially extend the innate plant immune system to a point where the rhizosphere immunity can fulfil all four core functions of a full immune system: pathogen prevention, recognition, response and homeostasis. We suggest that considering plant health from a meta-organism perspective will help in developing multidisciplinary pathogen management strategies that focus on steering the whole plant-microbe-soil networks instead of individual components. This might be achieved by bringing together the latest discoveries in phytopathology, microbiome research, soil science and agronomy to pave the way toward more sustainable and productive agriculture.

关键词： rhizosphere soil microbiome plant immunity microbial ecology plant health soilborne pathogens

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大鼠脊髓发育过程中时序转录组的发育时间模式和分子网络特征 Article

杨建, 赵莉莉, 易晟, 丁斐, 杨宇民, 刘炎, 王勇军, 刘梅, 薛成斌, 许莲, 龚蕾蕾, 王星辉, 张愉, 于彬, 明国丽, 顾晓松

《工程（英文）》 2021年第7卷第11期页码 1592-1602 doi: 10.1016/j.eng.2021.10.001

摘要：

目前对胎盘哺乳动物脊髓发育的分子网络特征我们知之甚少。这些特征对深入理解与再生相关的重要生物过程和组织工程研究非常必要。现在，借助于从胚胎期到成年期大鼠脊髓的大规模时序转录组分析取得了一些新的进展。研究发现发育早期波动的RNA表达水平反映了脊髓活跃的转录调控并可能启动了脊髓的早期模式发育。脊髓发育过程中由microRNA (miRNA)和转录因子（TF）构成的宏观调控网络在新生期前后存在切换现象（即“镶嵌模型”）。差异可变剪接事件提示了可变剪接可能是郎飞结发育的驱动力之一。我们的研究也支持了脊髓中先天免疫的发育与其内在生长能力之间存在负相关性。发育过程中的一些表观遗传学修饰很可能在不同发育阶段发挥各自的调控功能。G蛋白偶联受体（包括嗅觉受体）可能在发育的轴突生长中发挥多效性作用。该研究为脊髓发育领域提供了有价值的资源，并与越来越多的单细胞数据形成互补，也为开发新的脊髓损伤组织工程策略提供了组学基础。

关键词：发育基因表达模式先天免疫脊髓转录组

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Immunogenicity and protective immunity against otitis media caused by pneumococcus in mice of Hib conjugate

null

《医学前沿（英文）》 2016年第10卷第4期页码 490-498 doi: 10.1007/s11684-016-0470-y

摘要：

This study evaluated the immunogenicity and protective immunity of a Hemophilus influenzae b (Hib) polysaccharide conjugate vaccine with the pneumococcal surface adhesin A (PsaA) protein carrier in young mice. The Hib polysaccharide was conjugated with the rPsaA protein carrier, which was produced using recombinant DNA technology. A total of 15 young mice aged 3 weeks to 5 weeks were immunized with the conjugate vaccine, and another 15 young mice of the same age were immunized with the licensed Hib-tetanus toxoid (TT) vaccine. Furthermore, the third group of 15 young mice was inoculated with phosphate buffer saline as control. The immunized mice were inoculated with pneumococcus in the middle ear. Results showed that IgG antibody responses against both the PsaA protein and Hib polysaccharide were observed in the Hib-PsaA group. However, no statistical difference was observed in the titer of IgG against the Hib polysaccharide between Hib-PsaA and Hib-TT groups. The elimination rate of pneumococcus and the inflammation of the middle ear showed the effectiveness of protective immunity against otitis media caused by pneumococcus. Our results suggest that the Hib polysaccharide can be successfully conjugated with rPsaA via amide condensation. This new Hib-PsaA conjugate vaccine can induce both anti-PsaA and anti-Hib immune responses in young mice and elicit effective protection against acute otitis media caused by pneumococcus.

关键词： conjugate vaccine pneumococcal surface adhesin A Hemophilus influenzae b immunogenicity otitis media

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Antitumor immunity of human SART3 gene vaccine against mouse tumor

HE Yu, YANG Shuhua, LIU Yong, LI Tao

《医学前沿（英文）》 2008年第2卷第1期页码 51-57 doi: 10.1007/s11684-008-0010-5

摘要： To determine whether squamous cell carcinoma antigen recognized by human T cell 3 (SART3) gene can induce antitumor immunity against tumor cells which express the gene, we constructed mouse tumor cells expressing human SART3 (LM8-SART3) and carried out experiments . After subcutaneous injection with SART3 gene vaccine, cytotoxic T lymphocyte (CTL) activity was measured using Cell Counting Kit-8. As for the part, C3H mice were divided into several groups. One group was challenged with tumor cells after immunity. Another group was treated with the vaccine after tumor implantation. It was found that human SART3 DNA vaccine can elicit a specific CTL reaction from the mouse splenocytes. After vaccination, tumor occurrence and tumor growth speed was reduced. The vaccine also shows activity in tumor treatment. We conclude that the human SART3 DNA vaccine can induce antitumor ability against tumor cells expressing human SART3 (LM8-SART3) which may provide new possibilities in antitumor therapy.

关键词： antitumor therapy occurrence implantation DNA vaccine SART3 DNA

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Decitabine induces -mediated immune responses in p53-mutated triple-negative breast cancer: a clinical and translational study

《医学前沿（英文）》 doi: 10.1007/s11684-023-1016-8

摘要： p53 is mutated in half of cancer cases. However, no p53-targeting drugs have been approved. Here, we reposition decitabine for triple-negative breast cancer (TNBC), a subtype with frequent p53 mutations and extremely poor prognosis. In a retrospective study on tissue microarrays with 132 TNBC cases, DNMT1 overexpression was associated with p53 mutations (P = 0.037) and poor overall survival (OS) (P = 0.010). In a prospective DEciTabinE and Carboplatin in TNBC (DETECT) trial (NCT03295552), decitabine with carboplatin produced an objective response rate (ORR) of 42% in 12 patients with stage IV TNBC. Among the 9 trialed patients with available TP53 sequencing results, the 6 patients with p53 mutations had higher ORR (3/6 vs. 0/3) and better OS (16.0 vs. 4.0 months) than the patients with wild-type p53. In a mechanistic study, isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type p53. In the DETECT trial, decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line (upregulation by 16-fold) and the most responsive patient with TNBC. Our integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation triple-negative breast cancer decitabine DNMT1 IRF7 innate immune response

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HEMIPTERAN-TRANSMITTED PLANT VIRUSES: RESEARCH PROGRESS AND CONTROL STRATEGIES

《农业科学与工程前沿（英文）》 2022年第9卷第1期页码 98-109 doi: 10.15302/J-FASE-2021389

摘要：

About 80% of plant viruses are transmitted by specific insect vectors, especially hemipterans with piercing-sucking mouthparts. Many virus-transmitting insects are also important crop pests that cause considerable losses in crop production. This review summarizes the latest research findings on the interactions between plant viruses and insect vectors and analyzes the key factors affecting insect transmission of plant viruses from the perspectives of insect immunity, insect feeding, and insect symbiotic microorganisms. Additionally, by referring to the latest applications for blocking the transmission of animal viruses, potential control strategies to prevent the transmission of insect-vectored plant viruses using RNAi technology, gene editing technology, and CRISPR/Cas9+ gene-driven technology are discussed.

关键词： control strategies / feeding / immunity / insect vector / microorganism / plant virus

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Gut microbiota and its implications in small bowel transplantation

null

《医学前沿（英文）》 2018年第12卷第3期页码 239-248 doi: 10.1007/s11684-018-0617-0

摘要：

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBT and the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host–microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

关键词： gut microbiota small bowel transplantation acute rejection chronic rejection mucosal immunity biomarker microbiota-targeted therapy