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简介：补充系统对普通病原体在天生的防卫起一个关键作用。补充的激活导致柔韧、有效的解朊的串联，它通过有势力proinflammatory分子的生产在病原体以及在古典煽动性的反应的产生的opsonization和细胞溶解终止。然而，更最近，在有免疫力的反应的补充的角色由于连接补充激活到适应有免疫力的回答的观察被扩展了。补充是在允许综合主人防卫到病原的挑战的天生、适应的有免疫力的回答之间的一座功能的桥，这现在被欣赏。因此，它的函数的研究象主机免疫者反应的组织和组织一样允许卓见进主人病原体相互作用的分子的underpinnings。这评论试图总结在主人防卫上在天生、适应的有免疫力的回答和这些相互作用的后果补充戏的角色。

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简介：导出病毒的nucleic酸的细胞的察觉到为对病毒感染的早防卫是必要的。在最近的年里，包括周期的GMP安培synthase(cGAS)和gamma-interferon-inducible蛋白质(IFI16)，察觉到蛋白质的DNA的发现导致了房间怎么对带DNA染色体的到来的病原体唤起强壮的天生的有免疫力的回答的理解。发信号由DNA传感器刺激了取决于适配器蛋白质圈套(干扰素基因的激发器)，到启用抗病毒的蛋白质的表示，包括类型我干扰素。便于有效感染，病毒发展了大量避免策略，指向的主人DNA传感器，适配器蛋白质和抄写因素。在这评论，STING小径的导致病毒的激活上的当前的文学被介绍，我们讨论在这条抗病毒的小径指向不同的步的最近识别的病毒的避免机制。

简介：在抗原刺激之上，天真的T助手房间区分进不同的系达到专业化性质和受动器功能。TH17房间，CD4+受动器T房间的一个最近识别的系，对真菌和细胞外的细菌在有免疫力的防卫起一个关键作用，而且贡献许多自体免疫的条件的致病。TH17房间被在T房间表明小径和transcriptional管理者的一个复杂网络安排。当T房间内在的小径的参与广泛地被描述了时，我们开始就正在欣赏怎么TH17房间开发被外来的小径塑造，特别天生的有免疫力的信号。树枝状的房间(DC)，到天生的桥牌的最重要的房间类型和适应免疫，驱动器T由提供antigenic，costimulatory和cytokine的H17房间区别发信号。这被DC被天生、煽动性的信号的识别经由模式识别受体，cytokine受体和接着激活细胞内部的发信号网络的另外的immunomodulatory受体调停。特别地，p38α；地图kinase作为一条批评小径出现了编程序DC依赖的T由在DC集成多重有启发性的信号的H17房间区别。这里，我们在导出DC的天生的有免疫力的信号由驾驶TH17房间区别。

简介：原来由红女王晚进化的生物学家Leigh凡·瓦伦描述了假设安置在主人和他们的病原体之间的进化军备竞赛为在另外的种类上导致竞争优势的分离、遗传上编码的事件选择。有免疫力的避免策略的例子在整个哺乳动物的免疫系统和病原体的合作进化被看见，例如原子factor-κ的酶的inactivation；B由编码病原体的毒力因素发信号或主人翻译。如此的immunoevasive演习将被期望为天生的有免疫力的counterstrategies的进化选择。在我们主人免疫和微生物引起的致病的理解的最近的进展提供了卓见进特别天生的有免疫力的改编，称为的旁观者激活。旁观者激活作为警告并且指示附近的uninfected房间生产煽动性的调停人，的感染的房间的后果发生通过直接房间接触或paracrine的任何一个发信号。因此，旁观者激活能允许免疫系统克服病原体的能力缴在直接感染的房间的有免疫力的发信号。这评论与与人的健康和疾病相关的特定的病原体在感染期间在天生的免疫介绍旁观者激活和他们的新兴的角色的一般特点的概述给关于旁观者激活的最近的机械学的发现的细胞内部的病原体，以及例子。

简介：AbstractObjective:Mifepristone (RU486), one of the most common medications for artificial abortion, attenuates the immunoregulatory effects of progesterone. However, the specific immune regulatory mechanism of RU486 in abortion remains unknown. We intended to investigate the immunomodulatory effects of RU486 on abortion.Methods:Sixty female mice were divided into the control group (0 mg RU486) and RU486 group (2 mg/kg RU486). The uterus, peripheral blood, and spleen were obtained for isolation of specific cell types. The population and phenotype of immune cells in the decidua, peripheral blood, and spleen were analyzed using flow cytometry. Statistical differences between groups were determined using two-tailed t-test. For all statistical tests, P < 0.05 was considered statistically significant.Results:RU486 effectively induced abortion in pregnant mice, with a significantly higher number of decidual macrophages (dMφ) (control group = 25.55% ± 2.467%, RU486 group = 19.41% ± 1.423%; P < 0.05), especially the major histocompatibility complex IIhigh subset. No difference in Mφ number was observed in the spleen or peripheral blood. Moreover, the dMφ from mice with RU486-induced abortion displayed a remarkable activated phenotype, with increased expressions of inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin (IL)-12 but decreased expressions of arginase-1 and IL-10. We also found elevated levels of decidual CD4+ T-cells in the RU486 group that exhibited a higher level of the proinflammatory cytokine interferon-γ and a lower level of the anti-inflammatory cytokines, IL-4 and IL-10.Conclusions:We report a new mechanism of RU486-induced abortion via the regulation of innate cell Mφ activation and the adaptive response of CD4+ T-cells present in the decidua but not the periphery.

简介：干扰素规章的因素(IRF)3在病毒或细菌的侵略期间为chemokines和cytokines的transcriptional正式就职是批评的。kinases坦克有约束力的kinase(TBK)1并且IkappaBkinase(IKK)蔚罐头phosphorylateIRF3和玩的C终端部分在IRF3激活的重要角色。在这研究，我们显示出那另外一个kinase，c-Jun-NH2-terminalkinase(JNK)，它的N终端丝氨酸上的phosphorylatesIRF3173残余，和TAK1能经由JNK刺激IRF3phosphorylation。没有影响C终端phosphorylation，JNK特定的禁止者SP600125禁止N终端phosphorylation。另外，lipopolysaccharide(LPS)上的调停IRF3的基因表情或polyinosinic-cytidylic酸(polyI:C)处理被SP600125严重地损害，以及为IRF3激活的记者基因试金。进一步证实的TAK1击倒这些观察。有趣地，组成的活跃IRF3(5D)能被SP600125禁止；JNK1罐头synergizeIRF3(5D)的行动，然而并非S173A-IRF3(5D)变异。更重要地，polyI:没能戏剧性地导致变异的S173A和SP600125的phosphorylation的C废除了被polyI刺激的IRF3phosphorylation和dimerization:C。因此，这研究证明TAK1-JNK串联为IRF3功能被要求，除了TBK1/IKK蔚，揭开为激活mitogen的蛋白质(地图)的新机制调整天生的免疫的kinase。

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简介：AbstractObjective:This study was designed to evaluate whether p62/SQSTM1 (hereafter referred to as p62) is involved in the immune response of macrophages against challenge by Candida albicans (C. albicans).Methods:We cultured bone marrow-derived macrophages (BMDMs) to investigate the immune response to challenge by C. albicans. The p62 gene was knocked down by transfection with p62 small interfering RNA (siRNA) in the p62 siRNA group. BMDMs transfected with nonsense siRNA served as the negative control (NC) group. These two groups of BMDMs were challenged with C. albicans in vitro. We detected p62 expression through quantitative reverse transcription PCR and western blotting. The phagocytosis ability of BMDMs was evaluated by flow cytometry and microscopic examination using an Olympus FV1000 laser scanning confocal microscope. Moreover, we determined the level of reactive oxygen species (ROS) in BMDMs. The mRNA levels of proinflammatory cytokines were determined by quantitative reverse transcription PCR.Results:After stimulation by C. albicans, the relative expression of p62 mRNA was increased in a dose-dependent manner, the relative expression of p62 and the ratio of BMDMs to C. albicans is 1.893 ± 0.2156 (1:1, P < 0.05), 2.873 ± 0.4787 (1:3, P < 0.05) and 3.556 ± 0.2892 (1:5, P < 0.01). The p62 protein level was also increased. After transfection with p62 siRNA, the mRNA and protein levels of p62 were significantly decreased in BMDMs (P < 0.05). After 0.5, 1 and 2 hours of co-culture of BMDMs with C. albicans, flow cytometry showed that the phagocytosis rates of C. albicans by BMDMs were significantly lower in the p62 siRNA group than in the NC group (39.70 ± 1.69% vs. 55.23 ± 0.72%, 46.70 ± 0.89% vs. 60.80 ± 1.78%, 51.90 ± 0.98% vs. 64.43 ± 2.0%, respectively, all P < 0.05). Consistent results were seen in the production of ROS (4269 ± 392.6 vs. 13426 ± 1859.7, 4967 ± 721.2 vs. 13687 ± 2611.2, 7647 ± 1950.0 vs. 17719 ± 1814.2, respectively, all P < 0.05). The ROS levels were higher in BMDMs of the NC group than in BMDMs transfected with p62 siRNA at 0.5, 1, and 2 hours after treatment with C. albicans. BMDMs was co-cultured with C. albicans for 4 and 12 hours, the mRNA levels of interleukin-1β and interleukin-18 in NCs were also higher than p62 siRNA group, interleukin-1β: (6.14 ± 1.63 vs. 12.12 ± 0.54, 8.81 ± 0.86 vs. 26.2 ± 4.67, respectively, all P < 0.05), IL-18: (0.38 ± 0.02 vs. 0.97 ± 0.06, 0.44 ± 0.02 vs. 2.23 ± 0.46, respectively, all P < 0.05).Conclusion:p62 plays an important role in the process of phagocytosis in BMDMs challenged by C. albicans through ROS production and expression of proinflammatory cytokines.

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简介：最近的研究揭开了激活主人的二个发信号小径对病毒的感染的天生的免疫。小径之一利用像使用费的受体(TLR)的成员检测通过endocytosis进入内涵体的病毒的家庭。TLR小径通过最终导致抄写因素NF-kappaB，IRF3和IRF7的激活的几发信号的蛋白质导致干扰素生产。另外的抗病毒的小径为细胞内部的病毒的双strandedRNA把RNAhelicaseRIG-I用作受体。RIG-I通过最近识别的适配器蛋白质MAVS激活NF-kappaB和IRF，包含居住在mitochondrial膜的蛋白质的一个卡片领域。MAVS为抗病毒的天生的免疫是必要的，但是它也用作丙肝病毒(HCV)的一个目标，它采用病毒的朊酶劈开MAVS离开线粒体，从而允许HCV逃离主人免疫系统。

简介：效法传统的发展遗传，在最后15年的研究证明了对细菌和真菌的天生的免疫主要被二条NF-B信号转导小径，使用费和IMD管理。抗病毒的免疫看起来源自RNA干扰，而对parasitoids的抵抗被使用费发信号授与。规章的机制和大多数果蝇免疫基因的注解从功能的genomic导出的这些post-transcriptional的鉴定用“模型”学习病原体，未经触动的动物和房间线。D。当他们变得识别，melanogaster主人因此提供了能被用来学习回答到自然微生物引起、后生动物的病原体，以及测试选择和进化变化的想法的核心信息。这些分析具有到在主人抵抗理解另外的昆虫主人病原体相互作用的机制和变化的决定因素的一般重要性。

简介：Survivalratesformetastaticlungcancer,includingnon-smallcelllungcancer(NSCLC)andsmallcelllungcancer(SCLC),arepoorwith5-yearsurvivalsoflessthan5%.Theimmunesystemhasanintricateandcomplexrelationshipwithtumorigenesis;agroundswellofresearchontheimmunesystemisleadingtogreaterunderstandingofhowcancerprogressesandpresentingnewwaystohaltdiseaseprogress.Duetotheextraordinarypoweroftheimmunesystem—withitscapacityformemory,exquisitespecificityandcentralanduniversalroleinhumanbiology—immunotherapyhasthepotentialtoachievecomplete,long-lastingremissionsandcures,withfewsideeffectsforanycancerpatient,regardlessofcancertype.Asaresult,arangeofcancertherapiesareunderdevelopmentthatworkbyturningourownimmunecellsagainsttumors.Howeverdeeperunderstandingofthecomplexityofimmunomodulationbytumorsiskeytothedevelopmentofeffectiveimmunotherapies,especiallyinlungcancer.

简介：由模式识别受体(PRR)的病原体的天生的察觉到在在自我和非自我部件之间的天生的辨别起必要作用，导致天生的有免疫力的防卫和煽动性的回答的产生。天生的煽动性的反应的开始，激活和分辨率被相互作用的一个复杂网络在有免疫力、非有免疫力的系统的众多的细胞、分子的部件之中调停。当时一控制并且有益的天生的煽动性的反应是批评的因为病原体的消除和织物动态平衡，dysregulated或持续发炎的维护导致象长期的感染那样的病理学的条件，煽动性的自体免疫的疾病。在这评论，我们为天生的免疫和煽动性的回答的建立和规定在我们细胞、分子的机制的理解讨论一些最近的进展。

简介：AbstractObjective:In order to study the important role and molecular mechanism of Brevinin-2 family antimicrobial peptide Brevinin-2ISb in methicillin-resistant Staphylococcus aureus (MRSA) infection of Caenorhabditis (C.) elegans, and to find the optimal therapeutic concentration of Brevinin-2ISb.Methods:By using a C. elegans model and MRSA infection modelto study the therapeutic effect of different concentrations of Brevinin-2ISb on C. elegans. Real-time PCR was used for investigating the effect of Brevinin-2ISb on the downstream gene expression of DAF-2/DAF-16 innate immune pathway and the major virulence factor gene expression of MRSA. With protein activity tests to study the inhibitory effect of Brevinin-2ISb on MRSA virulence factor protein activity. Finally, laser confocal imaging was carried out to observe real-time expression and distribution of downstream antimicrobial proteins to further prove the effect of Brevinin-2ISb on the activation of DAF-2/DAF-16 pathway by in vivo imaging. All animal study procedures were approved by the Academic Committee at Xidian University and Xi’an Jiaotong University Animal Care and Use Committee, China (approval No. JGC201207) on July 15, 2017.Results:Host immunity was largely enhanced by Brevinin-2ISb, and the expression of staphylococcal enterotoxin genes, as well as virulence factors, was suppressed by Brevinin-2ISb. Indeed, the expression of many C. elegans innate immune genes, including lys-7, spp-1, K05D8.5 and C29F3.7, was induced by Brevinin-2ISb. In particular, robust, sustained expression of the antibacterial gene lys-7 was observed after Brevinin-2ISb treatment, resulting in increased protein levels. These effects correlated with a reduction in the MRSA-mediated death of the C. elegans host. Low concentrations of Brevinin-2ISb exhibited very low hemolytic activity, and may play a positive role in host innate immunity. Specifically, activation of the DAF-2/DAF-16 pathway appears to be essential for immune activation in C. elegans treated with Brevinin-2ISb. Based on the evolutionary conservation of innate immune pathways, our results suggest that Brevinin-2ISb not only has strong antibacterial activity, but may also enhance the innate immune response in humans. This study demonstrates that Brevinin-2ISb-related peptides are potential candidates for the development of novel anti-inflammatory or anti-microbial drugs.Conclusion:Antimicrobial peptide Brevinin-2ISb effectively inhibits MRSA at low concentration. This antimicrobial peptide can prolong the life of MRSA-infected C. elegans, has very low hemolytic activity and inhibits the activity and expression of various MRSA virulence factors. More importantly, Brevinin-2ISb activated the expression of antimicrobial genes downstream of DAF-2/DAF-16, which enhanced the MRSA resistance of C. elegans. This peptide could be used as the basis for developing new drugs to replace antibiotics.

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简介：Basedonimmuneclusteringandevolutionaryprogramming(EP),ahybridalgorithmtotraintheRBFnetworkisproposed.AnimmunefuzzyC-meansclusteringalgorithm(IFCM)isusedtoadaptivelyspecifytheamountandinitialpositionsoftheRBFcentersaccordingtoinputdataset;thentheRBFnetworkistrainedwithEPthattendstoglobaloptima.TheapplicationofthehybridalgorithminmultluserdetectionproblemdemonstratesthattheRBFnetworktrainedwiththealgorithmhassimplenetworkstructurewithgoodgeneralizationability.

简介：Exosomes,secretedbymanylivecells,aresmallnon-cellvesicleswithnanoparticle-gradesize.Inadditiontotheoriginalfunctionofdiscardingtheuselessfulmembranemolecules,exosomesareinvolvedinarangeofimmunoregulatoryfunctions.Dendriticcell-derivedexosomesandtumor-derivedexosomesarethebestcharacterizedvesicleswithpotentantitumoreffectbyefficienflyinducingimmuneresponse.Down-regtdationofimmuneresponseorinductionofimmunetoleranceisanotherinterestingfunctionofexosomes，Furtherfunctionalstudiesoftheexosomeswillshedlightontheapplicationofexosomes。