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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.

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

简介：昆虫的天生的免疫系统被划分成包括可溶的受动器分子的生产的体液的防卫和象被血球调停的吞噬作用和封装一样的细胞的防卫。这评论总结细胞的免疫反应的当前的理解。昆虫生产被形态学区分的血球的几种严重地区分的类型，分子并且反遗传因子的标记，和功能。在幼虫或nymph的阶段昆虫传播的区分的血球从二来源产生：在胚胎开始和中层联盟者期间生产的祖先房间导出造血的机关。造血作用和血球区别的规定也包含几条不同发信号小径。吞噬作用和封装要求血球首先作为外国认出一个给定的目标由下游的发信号和受动器回答的激活列在后面。很多体液、细胞的受体被识别了认出不同微生物和多细胞的寄生虫。接着，这些受体的激活刺激调整不同血球功能的很多条发信号的小径。最近的研究也作为为杀死不同外国侵略者要求的很多个体液的受动器分子的重要来源识别血球。

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。

简介：细菌的细胞内部的共生在昆虫是很普通的，有在支持生命和生物多样性的进化的重要后果。最近吸引了特别注意的细菌的组是可能在行星上代表最无所不在的endosymbiont的Wolbachiapipientis。W。pipientis是一克否定应尽细胞内部并且似母亲播送了l-proteobacterium，那能与节肢动物和线虫建立共生协会。在节肢动物，Wolbachiapipientis感染在Arachnida被描述了，在Isopoda并且主要在Insecta。他们包括Diptera，翘目，半翅类，Hymenoptera，直翅目和鳞翅目在几乎所有主要昆虫订单被报导了。提高它的传播，W。pipientis能由导致单性生殖，女性化，男性杀死和细胞质的不兼容操作主人复制。几聚合酶链反应调查显示了多达70%所有昆虫种类可以感染W。pipientis。怎么做W。pipientis设法变得在多样的昆虫主人种类确定了？这细胞内部的细菌的共生者种怎么在逃离宿主免疫反应是那么成功的？现在的评论在这块地里介绍最近的进展和进行中的科学努力。这域里的知识的当前的身体被总结，从可得到的genomic信息的展现被介绍，迄今为止未答复的问题在一次尝试被讨论介绍W的唯一的能力的一幅全面图画。pipientis将建立共生并且当躲避主人的免疫系统时，操作复制。

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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：肝炎B病毒(HBV)感染与传染virions和非传染的空表面抗原粒子的版本首先在hepatocytes发生在肝进血液。HBV复制是non-cytopathic。短暂感染运用几个月，和长期的感染的一堂功课经常是终生的。长期的感染能与肝硬化和hepatocellular癌导致肝失败。抵销anti-HBs抗体由在感染的主人包含感染的传播并且便于病毒的粒子的移动和破坏从HBV感染在恢复起一个关键作用，这通常被接受。然而，对病毒的抗原的T房间反应开始的有免疫力的反应在HBVinfection.The为病毒的清理和疾病致病也是重要的病毒的蛋白质，HBsAg，微粒HBcAg，和nonparticulateHBeAg的三种结构的形式，可以优先地得到不同Th房间子集。在不同HBV感染地位的anti-HBs，anti-HBc，和anti-HBe的不同IgG亚纲侧面被揭示。而且，在长期的搬运人的不同IgG亚纲侧面没随着不同中高音和著名计算机生产厂商层次变化并且可以反映刺激抗原之间的差别，有免疫力的反应，并且病毒的疾病的阶段并且在人的HBV感染的高风险为个人为疫苗和预防处理的使用提供基础。这评论阐明在短暂、坚持的感染期间导致的有免疫力的回答的详细理解，和在有HBV感染的病人的免疫疗法和immunodiagnosis的发展，和减少肝的可能的工具损坏。

简介：AbstractEffective prophylactic and therapeutic interventions are urgentlyneeded to address the coronavirus disease 2019 (COVID-19) pandemic. Various antiviral drugs have recently been tested. Type I interferon (IFN) is a regulatory protein involved in the innate immune response, with broad-spectrum antiviral activities and the ability to directly block viral replication and support the immune response to eliminate virus infection. Insufficient virus-induced type I IFN production is characteristic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, because SARS-CoV-2 suppresses the IFN response by interacting with essential IFN signaling pathways. Exogenous type I IFN is recommended for treating COVID-19. Unexpectedly however, angiotensin converting enzyme-2 (ACE2) receptor, which acts as a SARS-CoV-2 receptor, was shown to be stimulated by IFN, raising doubts about the suitability of IFN use. However, further studies have excluded concerns regarding IFN administration. Type I IFNs, including IFN-α1b, have been used clinically as antiviral drugs for many years and have shown strong antiviral activity against SARS-CoV-2 in vitro. Preliminary clinical studies of type I IFNs, especially when delivered via aerosol inhalation, have demonstrated efficacy for the treatment and prevention of COVID-19. Randomized controlled trials of IFN for COVID-19 treatment are ongoing.

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。

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简介：Multiplesclerosis(MS)isachronicimmune-mediatedinnammatory-demyelinatingdisorderofthecentralnervoussystem,withastrongneurodegenerativecomponent.ThequestionwhetherneurodegenerationinMSisindependentorrelatedtoneuroinflammationhasbeenlongdebated,butnotyetfullyclarified.Furthermore,littleisstillknownonhowneuroinflammationandneurodegenerationinMSarerelatedtopotentialregenerativeprocesses.Inthisperspective,webrieflydiscussmainclinical,pathologicalandexperimentalevidenceontherelationshipbetweenneuroinflammationandneurodegenerationinMS,andontheirconnectionwithregeneration.WediscussthattheseprocessesinMSmightrepresentintercorrelatedmanifestationsoftheimmuneresponse,especiallyoftheinnateimmunity.

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：AbstractHost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in children, are still under investigation. Children with coronavirus disease 2019 (COVID-19) constitute a significant study group of immune responses as they rarely present with severe clinical manifestations, require hospitalization, or develop complications such as multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection. The deciphering of children's immune responses during COVID-19 infection will provide information about the protective mechanisms, while new potential targets for future therapies are likely to be revealed. Despite the limited immunological studies in children with COVID-19, this review compares data between adults and children in terms of innate and adaptive immunity to SARS-CoV-2, discusses the possible reasons why children are mostly asymptomatic, and highlights unanswered or unclear immunological issues. Current evidence suggests that the activity of innate immunity seems to be crucial to the early phases of SARS-CoV-2 infection and adaptive memory immunity is vital to prevent reinfection.

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