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A Vesicular Stomatitis Virus-Based Vaccine Carrying Zika Virus Capsid Protein Protects Mice from Viral Infection

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Virologica Sinica 2019年第1期34卷 106-110页

作者： Xiaodan Shi Jingping Hu Jing Guo Chuanjian Wu sidong xiong Chunsheng Dong Jiangsu Key Laboratory of Infection and Immunity The Institutes of Biology and Medical SciencesSoochow University

Dear Editor,Zika virus (ZIKV) is a mosquito-borne virus that belongs to the Flavivirus family along with dengue virus (DENV),yellow fever virus, West Nile virus, and Japanese encephalitis virus (Ming et al. 2016). ZIKV is a singlestranded positive-sense RNA virus encoding three structural proteins, including nucleocapsid protein C, prM/M,envelope glycoprotein E, and seven non-structural proteins.Since 2015.

关键词： VSV A Vesicular Stomatitis Virus-Based Vaccine Carrying Zika Virus Capsid Protein Protects Mice from Viral Infection

Mycobacterium tuberculosis gene SapM inhibits autophagy in human embryonic kidney cell line 293A

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Mycobacterium tuberculosis gene SapM inhibits autophagy in h...

第十一届全国免疫学学术大会

作者： Zhang Wei Dong Yuanshu Xiong sidong Institutes of Biology and Medical Sciences Soochow University

Background:Tuberculosis(TB) is a permanently respiratory disease which has afflicted human life and health.Autophagy is a cytoplasmic maintenance process which plays a pivot role against mycobacterium tuberculosis(Mtb).It has been reported that Sap M(also named Rv3310),a secreted acid phosphatase of Mtb,inhibits host cell autophagy by blocking autophagosome-lysosome fusion,but its role in the initiation of autophagy is unknown.Objective:Investigate the role of Mtb gene Sap M in regulating the initiation of autophagy in HEK293 A cells.Methods:We constructed the plasmid p FLAG-CMV2-Sap M to express Mtb gene Sap M in eukaryotic cells,and established 293 A cell line that stably expressing Sap M and GFP-LC3(Sap M-GFP-LC3 293A) by co-transfection.Sap M-GFPLC3 293 A cells and Vector-GFP-LC3 293 A cells were treated with autophagy inducer rapamycin or starvation,with or without chloroquine,and LC3 Ⅱ protein levels were detected by western blot,flow cytometry,or Fluorescence microscopy.Results:With Rapamycin treatment,LC3 II level was obviously lower in cells overexpressing Sap M compared to that in vector control cells.Moreover,after blocking autophagosome-lysosome fusion by chloroquine,the number of rapamycin induced GFP-LC3 punta in Sap M-GFP-LC3 group were dramatically lesser than that in vector group.Similar results were observed in starvation-induced autophagy.Conclusions:Our results indicated that Sap M inhibited a complete autophagic flux in HEK293 A cells and it suppressed the initiation of autophagy.These findings facilitated our understanding of the mechanisms how Sap M promoting the infection of Mtb,and may provide a new target for potential vaccines or drugs against tuberculosis.

关键词： Tuberculosis SapM Autophagy

HIV-1 hijacks host karyopherin KPNA2 for efficient nuclear import in macrophages

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HIV-1 hijacks host karyopherin KPNA2 for efficient nuclear i...

第十一届全国免疫学学术大会

作者： Dong Chunsheng Tang Shengjie Xiong sidong The Institutes of Biology and Medical Sciences Soochow University

Objective: Monocytes from peripheral blood are insensitive for HIV-1 infection. However, when monocytes differentiate into macrophages, they show an increased sensitivity for HIV infection. Our previous RNAseq analysis demonstrated more than 1100 host genes including KPNA2 were different expressed in monocytes and monocytes derived macrophages(MDM) including KPNA2. In the present study, we investigated the role of KPNA2 in HIV replication. Methods: 293 T cells were infected with HIV single cycle luciferase reporter virus. KPNA2 expression was down-regulated with siRNA. The HIV replication was measured by lucifierase activity in the cell lysates. HIV reverse transcription and nuclear import were measured by the quantitative PCR for Late-RT and 2-LTR products, repectively. Results: KPNA2 was up-regulated in the monocytes to macrophages differentiation. The siRNA mediated knockdown of KPNA2 demonstrated that it was important for HIV replication. Quantitative 2-LTR PCR revealed that KPNA2 enhanced the HIV pre-integration complex nuclear imort. Conclusion: Taken together, our results showed that KPNA2 may be one of the key factors contributing to the sensitivity of HIV replication during monocytes to macrophages differentiation.

关键词： HIV KPNA2 Nuclear Import macrophages

Bacillus Calmette Guerin induces trained immunity in murine BMDMs

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Bacillus Calmette Guerin induces trained immunity in murine ...

第十一届全国免疫学学术大会

作者： Peng Zhangli Yue yan Xiong sidong Soochow University

Background:Bacille Calmette-Guerin(BCG),the vaccine used for the prevention of tuberculosis(TB) has continuously been in use for more than 90 years.In addition to its protection effect against TB,BCG has attracted more and more attention and interests because of its potent non-specific immune-enhancing ability.It has been showed that BCG could obviously enhance host innate immune responses against tumors,impact severity and prognosis of many allergic,and many auto-immune diseases.This "memory-like" phenomenon of innate immune responses was termed as "trained immunity".So far experiments of BCG-induced trained immunity are mainly performed on monocytes.Considering that monocytes could further enter peripheral tissues,differentiate into macrophages,which are responsible for the activation and modulation of subsequent immune responses.So it is important to explore whether BCG could induces trained immunity in macrophages or not.Objective:To investigate whether macrophages can be trained by BCG or not.Methods:BMDMs were primed with different doses of BCG for 24 h,and then washed to remove all stimuli.After resting for 5 days,cells were stimulated with LPS.The levels of proinflammatory cytokines were determined by enzymelinked immunosorbent assays(ELISA).Results:Compared with BMDMs without BCG priming,cells priming with BCG produced significantly higher levels of proinflammatory cytokines(TNF-α and IL-6).The level of TNF-α in BMDMs without BCG priming was 530 pg/ml,while with BCG priming,the level of TNF-α could significantly increased to 1200 pg/ml.Similar phenomenon was alsoobserved in IL-6,in which was 800 pg/ml in BMDMs without BCG priming,but increased to 1400 pg/ml with BCG priming.Conclusion:BCG could efficiently induce trained immunity in the differentiated macrophages(BMDMs),our data further extend of the ‘‘trained immunity’’ phenomenon from monocytes to macrophages and this might help the design of further vaccination.

关键词： Bacille Calmette-Guerin macrophages trained immunity

Mechanisms of molecular recognition and cellular regulation involved in Self-DNA induced SLE

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Mechanisms of molecular recognition and cellular regulation ...

第十届全国免疫学学术大会

作者： sidong xiong Institutes of Biology and Medical Sciences (IBMS) Soochow University

Systemic lupus erythematosus(SLE)is the prototype of autoimmune disease and the mechanisms underlying the disease have not yet been elucidated.Here we reported that a murine model of SLE induced by syngeneic activated lymphocytederived DNA(ALD DNA)was established.The syngeneic and hypomethylated apoptotic but not necrotic DNA was

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CD4^(+) T cell-released exosomes inhibit CD8^(+) cytotoxic T-lymphocyte responses and antitumor immunity

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Cellular & Molecular Immunology 2011年第1期8卷 23-30页

作者： Haifeng Zhang Yufeng Xie Wei Li Rajni Chibbar sidong xiong Jim Xiang Research Unit Health Research DivisionSaskatchewan Cancer AgencyDepartment of Oncology and ImmunologyUniversity of SaskatchewanSaskatoonSask.Canada Research Unit Health Research DivisionSaskatchewan Cancer AgencyDepartment of PathologyUniversity of SaskatchewanSaskatoonSask.Canada Institute of Biology and Medical Sciences Soochow UniversitySuzhouChina

T cells secrete bioactive exosomes(EXO),but the potential immunoregulatory effect of T-cell EXO is largely unknown.In this study,we generated activated ovalbumin(OVA)-specific CD4^(+) T cells in vitro via coculture of OVA-pulsed dendritic cells(DC_(OVA))with naive CD4^(+) T cells derived from OVA-specific T-cell receptor(TCR)transgenic OTII mice.CD4^(+) T-cell EXO were then purified from the CD4^(+) T-cell culture supernatants by differential ultracentrifugation.CD4^(+) T-cell EXO exhibited the‘saucer’shape that is characteristic of EXO with a diameter between 50 and 100 nm,as assessed by electron microscopy,and contained the EXO-associated proteins LAMP-1,TCR and lymphocyte function associated antigen-1(LFA-1),as determined by western blot.Flow cytometric analysis showed that CD4^(+) T-cell EXO expressed CD4^(+) T-cell markers(CD4,TCR,LFA-1,CD25 and Fas ligand),but to a lesser extent than CD4^(+) T cells.We demonstrated that DC_(OVA) took up CD4^(+) T-cell EXO via peptide/major histocompatibility complex(pMHC)II/TCR and CD54/LFA-1 interactions.OVA-specific CD4^(+) T-cell EXO from OTII mice,but not ConA-stimulated polyclonal CD4^(+) T-cell EXO from wild-type C57BL/6 mice inhibited DC_(OVA)-stimulated in vitro CD4^(+) T-cell proliferation and in vivo CD81 cytotoxic T lymphocyte(CTL)responses and antitumor immunity against OVA-expressing B16 melanoma BL6-10OVA cells.In addition,EXO derived from a T-cell hybridoma cell line,MF72.2D9,expressing an OVA-specific CD4^(+) TCR,had a similar inhibitory effect as OTII CD4^(+) T-cell EXO on CTL-mediated antitumor immunity.Taken together,our data indicate that antigen-specific T-cell EXO may serve as a new type of immunosuppressive reagent for use in transplant rejection and treatment of autoimmune diseases.

关键词： antitumor immunity CTL T-cell exosome

A novel oncolytic virus engineered with PD-L1 scFv effectively inhibits tumor growth in a mouse model

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Cellular & Molecular Immunology 2019年第9期16卷 780-782页

作者： Chuanjian Wu Manman Wu Minglong Liang sidong xiong Chunsheng Dong Jiangsu Key Laboratory of Infection and Immunity The Institutes of Biology and Medical SciencesSoochow University199 Ren-Ai RoadSuzhou 215123 JiangsuChina

The adoptive transfer of engineered chimeric antigen receptor(CAR)T cells has yielded impressive clinical results for targeting hematological cancers.1 However,the advancement of CAR T-cell therapy in solid tumors remains limited,due to the scarcity of tumor antigens that are deemed safe for targeting.Moreover,the requirement of patient-specific autologous T cells for the current standard treatment has also hampered its application.Oncolytic virus(OV)therapy has been classified as another form of novel immunotherapy.

关键词： therapy clinical engineered

C-reactive protein functions as a negative regulator of macrophage activation induced by apoptotic DNA

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Protein & Cell 2011年第8期2卷 672-679页

作者： Weijuan Zhang Yanxing Cai Wei Xu sidong xiong Institute for Immunobiology and Department of Immunology Shanghai Medical CollegeFudan UniversityShanghai 200032China Jiangsu Key Laboratory of Infection and Immunity Institutes of Biology and Medical SciencesSoochow UniversitySuzhou 215123China

C-reactive protein(CRP),an acute-phase protein with an ability to bind to nuclear antigen,has been reported to regulate cytokine secretion and modulate immune responses.We previously reported that activated syngeneic lymphocyte-derived apoptotic DNA(apopDNA)could induce macrophage activation and contribute to the initiation and progression of lupus nephritis.It is reasonable to hypothesize that CRP might regulate apopDNA-induced macrophage activation.Herein,CRP was shown to promote macrophage-mediated apopDNA uptake by binding to apopDNA(CRP/apopDNA complex).Notably,CRP/apopDNA treatment inhibited the production of inflammatory cytokines and chemokines by macrophages which could be induced by apopDNA alone.Further coculture and transwell studies revealed that CRP/apopDNA-induced macrophages prohibited apopDNA-induced macrophage activation in an IL-10 dependent manner.These results provide insight into the potential mechanism of CRP regulatory activity in macrophage activation induced by apopDNA in the context of lupus nephritis and other autoimmune diseases.

关键词： C-reactive protein(CRP) macrophage activation autoimmunity systemic lupus erythematosus(SLE) lupus nephritis

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地方高校“双一流”建设:何以成就世界一流

大学与学科 2020年第1期1卷 186-193页

作者：熊思东苏州大学苏州215006

创建世界一流大学,既是时代的呼唤,也是大学的责任与使命。作为我国高等教育体系的重要组成部分,地方高校始终坚持树立一流意识,围绕一流目标,贯彻一流标准,着力推进一流学科建设,逐渐具备了较强的竞争力和较大的影响力,为迈向世界一流... 详细信息

创建世界一流大学,既是时代的呼唤,也是大学的责任与使命。作为我国高等教育体系的重要组成部分,地方高校始终坚持树立一流意识,围绕一流目标,贯彻一流标准,着力推进一流学科建设,逐渐具备了较强的竞争力和较大的影响力,为迈向世界一流打下了一定基础。面向未来,地方高校要充分把握"双一流"建设带来的历史机遇和广阔空间,重新定义地方高校的视野、格局与边界,探索迈向世界一流的新路径,推动我国高等教育强国战略目标早日实现。

关键词：地方高校 “双一流”建设路径学科建设一流学科