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cFLIPS regulates alternative NLRP3 inflammasome activation in human monocytes

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Cellular & Molecular Immunology 2023年第10期20卷 1203-1215页

作者： Yuhui Gao Shi Yu mengdan Chen Xun Wang Lei Pan Bin Wei guangxun meng School of Life Sciences Shanghai UniversityShanghai200444China The Center for Microbes Development and HealthCAS Key Laboratory of Molecular Virology&ImmunologyUniversity of Chinese Academy of SciencesShanghai200031China Shanghai Blood Center Shanghai200051China Pasteurien College Soochow UniversitySuzhou215006JiangsuChina Nanjing Advanced Academy of Life and Health Nanjing211135JiangsuChina Department of Basic Research Guangzhou LaboratoryGuangzhou International Bio-lslandGuangzhou 510o05 GuangdongChina

The innate immune responses,including inflammasome activation,are paramount for host defense against pathogen *** contrast to canonical and noncanonical inflammasome activation,in this study,heat-killed gram-negative bacteria(HK bacteria)were identified as single-step stimulators of the NLRP3 inflammasome in human monocytes,and they caused a moderate amount of IL-1βto be released from *** course experiments showed that this alternative inflammasome response was finished within a few *** analysis showed that the intrinsically limited NLRP3 inflammasome activation response was due to the negative regulation of caspase-8 by the short isoform of cFLIP(cFLIPs),which was activated by NF-κ*** contrast,overexpressed cFLIPS,but not overexpressed cFLIPL,inhibited the activation of caspase-8 and the release of IL-1βin response to HK bacteria infection in human ***,we demonstrated that TAK1 activity mediated the expression of cFLIPs and was upstream and essential for the caspase-8 cleavage induced by HK bacteria in human *** functional specificity of cFLIPs and TAK1 revealed unique responses of human monocytes to a noninvasive pathogen,providing novel insights into an alternative regulatory pathway of NLRP3 inflammasome activation.

关键词： cFLIPS gram-negative bacteria NLRP3 inflammasome human monocyte

The NLRP3 Inflammasome activation in human or mouse cells,sensitivity causes puzzle

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Protein & Cell 2013年第8期4卷 565-568页

作者： Hongbin Wang Liming Mao guangxun meng Unit of Innate Immunity Key Laboratory of Molecular Virology and ImmunologyInstitut Pasteur of ShanghaiShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200025China Graduate University of Chinese Academy of Sciences Beijing 100039China

SIGNAL 1 ALONE IS ENOUGH TO ACTIVATE THE NLRP3 INFLAMMAOSME IN HUMAN CELLS According to our current understanding,the NLR family,pyrin domain containing 3(NLRP3)infl ammasome activation is generally a two-step *** fi rst step is priming,in which pathogen associated molecular patterns(PAMPs)such as LPS or pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α)induced NF-κB activation provides synthesis of pro-IL-1βand NLRP3 *** priming step is considered as signal 1,which makes the cell ready for a second strike to assemble the infl *** danger signals such as ATP and MSU provide the signal 2 that promotes formation of the NLRP3 infl ammasome and activates *** of these 2 steps are required in mouse macrophages for the NLRP3 inflammasome activation(Dinarello,2007).

关键词： NLRP3 activation cytokines

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模式识别受体对肠道菌群稳态的影响

中国科学：生命科学 2023年第5期53卷 571-581页

作者：孟广勋中国科学院上海巴斯德研究所微生物、发育与健康研究中心中国科学院分子病毒与免疫重点实验室上海200031 中国科学院大学北京101408

大量共生微生物定植于人的肠道、肺、皮肤、生殖道等黏膜和屏障器官,与免疫系统和上皮屏障系统存在动态、复杂的相互作用,对维持健康至关重要.共生菌群通过其多种组分和代谢物影响免疫系统的发育和功能,免疫系统则通过多种免疫细胞、免... 详细信息

大量共生微生物定植于人的肠道、肺、皮肤、生殖道等黏膜和屏障器官,与免疫系统和上皮屏障系统存在动态、复杂的相互作用,对维持健康至关重要.共生菌群通过其多种组分和代谢物影响免疫系统的发育和功能,免疫系统则通过多种免疫细胞、免疫因子调控共生菌群的发育、定植和功能.免疫系统包括天然免疫和获得性免疫系统两部分,而天然免疫系统处于和共生微生物互作或响应病原微生物感染的前沿.本文综述了宿主天然免疫系统的模式识别受体(pattern recognition receptor,PRR)的功能缺失或异常对肠道菌群的影响,主要包括炎症小体、NOD样受体(NOD-like receptor,NLR)、Toll样受体(Toll-like receptor,TLR)、C型凝集素受体(C-type lectin receptor,CLR)、维甲酸诱导基因样受体(RIG-I-like receptor,RLR)对肠道菌群的调控,并指出遗传和环境因素在塑造肠道菌群中的协同作用.

关键词：天然免疫模式识别受体炎症小体黏膜免疫感染肠道微生物群稳态

TAK1 Deficiency in Macrophages Increases Host Susceptibility to Leishmania Infection

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感染微生物与疾病(英文) 2023年第3期5卷 127-136页

作者： Xiankai Cao Kossiwa C.Kokou Shi Yu mengdan Chen Junling Niu HervéLecoeur Eric Prina Gerald F.Späth guangxun meng The Center for Microbes Development and HealthCAS Key Laboratory of Molecular Virology&ImmunologyUniversity of Chinese Academy of SciencesShanghaiChina Institute Pasteur Paris City UniversityINSERM U1201Molecular Parasitology and Signalling UnitParisFrance Pasteurien College Soochow UniversitySuzhouChina Nanjing Advanced Academy of Life and Health NanjingChina.

Leishmania parasites mainly infect macrophages and may cause severe immunopathologies in their host,which are called *** the current work,we infected human and mouse macrophages in vitro with Leishmania major,an etiological agent of cu-taneous leishmaniasis,and found that inhibition or deletion of the transforming growth factorβ–activated kinase 1(TAK1)gene re-sulted in increased parasite *** vivo,following a challenge with ***,mice with a macrophage-specific deletion of TAK1 showed increased clinical signs and higher parasite loads compared with wild-type ***1 deficiency in mouse macro-phages led to biased Th2 cell responses during the acute stage of infection,characterized by a decrease in interferon-γexpression,and increased expression of IL-4,IL-5 and ***,we found that,in the late stage of *** infection,excessive Th2-related cytokines led to high arginase 1 expression in mouse tissues and a significant reduction of NO production both locally and system-ically,resulting in compromised control of *** findings suggest that TAK1 plays a vital role in host resistance to Leish-mania infection.

关键词： TAK1 macrophage Leishmania major arginase 1 nitric oxide

Cellular localization of NLRP3 inflammasome

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Protein & Cell 2013年第6期4卷 425-431页

作者： Yan Wang Chen Yang Kairui Mao Shuzhen Chen guangxun meng Bing Sun Key Laboratory of Molecular Virology and Immunology Institute Pasteur of ShanghaiShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200025China State Key Laboratory of Cell Biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of ScienceShanghai 200031China

Infl ammasome is a large protein complex activated upon cellular stress or microbial infection,which triggers maturation of pro-inflammatory cytokines interleukin-1βand interleukin-18 through caspase-1 ***-like receptor family protein 3(NLRP3)is the most character-ized infl ammasome activated by various ***,the mechanism of its activation is unclear and its exact cellular localization is still *** examined the potential co-localization of NLRP3 infl ammasome with mi-tochondria and seven other organelles under adenosine triphosphate,nigericin or monosodium urate stimulation in mouse peritoneal macrophages using confocal micros-copy *** results revealed that the activated endogenous apoptosis-associated speck-like protein containing a CARD(ASC)pyroptosome forms in the cyto-plasm and co-localizes with NLRP3 and caspase-1,but not with any of the organelles *** study indicates that the ASC pyroptosome universally localizes within the cytoplasm rather than with any specifi c organelles.

关键词： NLRP3 inflammasome ASC pyroptosome confocal microscopy cytoplasmic

Pannexin-1 infl uences peritoneal cavity cell population but is not involved in NLRP3 infl ammasome activation

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Protein & Cell 2013年第4期4卷 259-265页

作者： Hongbin Wang Yue Xing Liming Mao Yi Luo Lishan Kang guangxun meng Unit of Innate Immunity Key Laboratory of Molecular Virology and ImmunologyInstitut Pasteur of ShanghaiShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesShanghai 200025China Beijing Novo Nordisk Pharmaceuticals Science and Technology Co. Ltd.29 Life Science Park RoadBeijing 102206China

Pannexin-1(Panx1)forms nonselective large channel in cell plasma membrane and has been shown to be associated with NLRP3 inflammasome activation,ATP release and phagocytes *** the current study,by manipulation of Panx1 expression in human myeloid cells and application of Panx1 defi cient mice,we failed to fi nd a correlation between Panx1 and NLRP3 infl ammasome activation,although an interaction between these two proteins was ***,in thioglycollate induced peritonitis,Panx1 defi cient mice showed much more phagocytes *** analyses showed that mice defi cient for Panx1 exhibited enlarged F4/80^(low)Gr1-Ly6C-cell population in the *** study thus reveals an important role for Panx1 in regulation of peritoneal cell population and peritonitis development.

关键词： innate Immunity inflammasome NLRP3 Pannexin-1 peritonitis

Human pathogenic fungus Trichophyton schoenleinii activates the NLRP3 inflammasome

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Protein & Cell 2013年第7期4卷 529-538页

作者： Hua Li Shuxian Wu Liming Mao Guowei Lei Liping Zhang Ailing Lu Liguo An Guiwen Yang Paride Abliz guangxun meng College of Life Science Shandong Normal UniversityJinan 250014China Unit of Innate Immunity Key Laboratory of Molecular Virology and ImmunologyInstitut Pasteur of ShanghaiShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200025China Department of Dermatology The First Hospital of Xinjiang Medical UniversityUrumqi 830054China

The fungus Trichophyton schoenleinii(***)is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and ***-man innate immune system plays an important role in combating with various pathogens including *** inflammasome is one of the most critical arms of host innate immunity,which is a protein complex controlling maturation of IL-1β.To clarify whether *** is able to activate the infl ammasome,we analyzed human monocytic cell line THP-1 for IL-1βproduction upon infec-tion with *** strain isolated from Tinea favosa patients,and rapid IL-1βsecretion from THP-1 cells was ***,applying competitive inhibitors and gene specifi c silencing with shRNA,we found that ***-oenleinii induced IL-1βsecretion,ASC pyroptosome for-mation as well as caspase-1 activation were all dependent on *** B activity,ROS production and K+effl ux were required for the infl ammasome activation by *** data thus reveal that the NLRP3 infl am-masome plays an important role in host defense against ***,and suggest that manipulating NLRP3 signaling can be a novel approach for control of diseases caused by *** infection.

关键词： innate immunity inflammasome NLRP3 Trichophyton schoenleinii infection

Celastrol specifically inhibits the activation of NLRP3 inflammasome

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Science China(Life Sciences) 2018年第3期61卷 355-357页

作者： Xuesong Sang Yihui Chen Wei Chen Jing Xie guangxun meng Jin Zhong Taisheng Li Ailing Lu CAS Key Laboratory of Molecular Virology & Immunology Institute Pasteur of Shanghai Chinese Academy of Sciences Shanghai 200031 China School of Life Sciences Shanghai University Shanghai 200444 China Department of Infectious Diseases Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100730 China Clinical Immunology Center Chinese Academy of Medical Sciences Beijing 100730 China

Dear Editor,Inflammasomes are vital components of the innate immune system that survey microbial infections or sterile challenges in the cytosol(de Zoete et al.,2014).A typical inflammasome is composed of a sensor pro... 详细信息

关键词： apoptosis 蛋白质组成激活免疫系统微生物传感器适配器受体

MXene supported PtCo bimetallic catalyst for hydrogen evolution in acidic conditions

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Frontiers in Energy 2024年第3期18卷 369-377页

作者： guangxun CHEN Jian-hua ZHANG Kai-Ling ZHOU Yang YANG Haoxiang MA Yuhong JIN Jingbin LIU Hao WANG Faculty of Materials and Manufacturing Beijing University of TechnologyBeijing 100124China Institute of Deep-Sea Science and Engineering Chinese Academy of SciencesSanya 572000China

Using the electrochemical technology to split water molecules to produce hydrogen is the key to obtain green hydrogen for solving the energy crisis. The large-scale application of hydrogen evolution reaction (HER) in water dissociation requires a highly active catalyst. In this paper, the highly dispersed PtCo bimetallic nanoparticles loading on MXene (PtCo/MXene) were prepared by using a step-to-step reduction strategy. The mentioned PtCo/MXene catalyst exhibits a high current density of −100 mA/cm2 in an acidic medium with just a 152 mV overpotential. In addition, the PtCo/MXene catalyst also displays a superior stability. Computational analysis and experimental testing demonstrate that the electronic interaction between Pt and Co can effectively modify the electronic structure of the active site, thereby enhancing the inherent catalytic performance of the material. More importantly, MXene two-dimensional nanosheets can expose more active sites because of their large specific surface area. Furthermore, MXene substrate with excellent electrical conductivity and harmonious interfaces between PtCo and MXene enhance charge transfer efficiency and lower the reaction activation energy.

关键词： MXene PtCo bimetallic hydrogen evolution reaction(HER)