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Divergent Primary Immune Responses Induced by Human Immunodeficiency Virus-1 gp120 and Hepatitis B Surface Antigen Determine Antibody Recall Responses

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Virologica Sinica 2018年第6期33卷 502-514页

作者： Li Yuan Wen-Jiang Chen Jia-Ye Wang Yan Li Dan Tian Ming-Xia Wang Hao-Tong Yu Ying-Chu Xu Di Li Min Zhuang Hong Ling department of Microbiology Harbin Medical University Heilongjiang Provincial Key Laboratory of infection and Immunity Key Laboratory of Pathogen Biology Wu Lien-Teh Institute Harbin Medical University department of Immunology Harbin Medical University

The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen(HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper(Tfh) cells, germinal centers,and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death(PD)-1^+T cells, greater major histocompatibility complex II expression on B cells, comparable activated B cells, but weaker germinal center(GC)reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1^+T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env.

关键词： Human immunodeficiency virus type 1 envelope Hepatitis B surface antigen(HBsAg) Immune memory Primary immune response Programmed death-1(PD-1)

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Staying home or leaving for a party:tissue-dependent choices of tissue-resident memory T cells

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Cellular & Molecular Immunology 2022年第6期19卷 651-652页

作者： Klaas P.J.M.van Gisbergen Joke M.M.den Haan department of Hematopoiesis Sanquin Research and Landsteiner LaboratoryAmsterdam UMCUniversity of Amsterdam1066CXAmsterdamThe Netherlands department of Molecular Cell Biology and Immunology Cancer Center AmsterdamAmsterdam Institute for Infection and ImmunityAmsterdam UMCVrije Universiteit AmsterdamAmsterdamThe Netherlands

CD8+T cells differentiate into different types of memory T cells after priming in the lymphoid organs.Central memory T cells selectively express lymph node homing markers and recirculate between the blood and the secondary lymphoid organs.Effector memory T cells lack lymph node homing capacity,mainly circulate in the blood,and may enter peripheral tissues.The third subset consists of tissue-resident memory T(Trm)cells that express CD69 and adhesion molecules such as CD11a,CD103,and CD49a that prevent tissue egress.

关键词： organs lymphoid CD69

Inducible expression of endomorphins in murine dendritic cells

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Neural Regeneration Research 2012年第35期7卷 2811-2817页

作者： Xiaohuai Yang Hui Xia Yong Chen Xiaofen Liu Cheng Zhou Qin Gao Zhenghong Li department of Urinary Surgery First Hospital of Bengbu Medical College Anhui Key Laboratory of infection & Immunity Bengbu Medical College department of Physiology Bengbu Medical College

Bone marrow precursor cells were extracted from C57BL/6J mice aged 7-8 weeks, and dendritic cells were purified using anti-CD1 lc （a specific marker for dendritic cells） antibody-coated magnetic beads. Immunofluorescence staining revealed that the expression levels of endomorphin-1 and endomorphin-2 were upregulated in dendritic cells activated by lipopolysaccharide. An enzyme Jmmunoassay showed that lipopolysaccharide and other Toll-like receptor ligands promoted the secretion of endomorphin-1 and endomorphin-2 from activated dendritic cells. [3H]-thymidine incorporation demonstrated that endomorphin-1 and endomorphin-2 both inhibited the proliferation of T lymphocyte induced by activated dendritic cells. Furthermore, this immunosuppressive effect was blocked by CTOP, a specific antagonist of IJ-opioid receptors. Our experimental findings indicate that activated dendritic cells can induce the expression and secretion of endomorphins, and that endomorphins suppress T lymphocyte proliferation through activation of iJ-opioid receptors.

关键词： dendritic cells endomorphin I J-receptor antigen-presenting cell nerve immunization neuralregeneration

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Prevalence and risk factors for bone mineral density changes in antiretroviral therapy-naive human immunodeficiency virus-infected adults:a Chinese cohort study

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Chinese Medical Journal 2020年第24期133卷 2940-2946页

作者： Yong-Qin Zeng Jiang Xiao Cui-Lin Li Yu Wang Ling Zhang Xiao-Li Pang Di Wang Juan Du Hong-Xin Zhao Department of Infection Beijing Ditan HospitalPeking UniversityBeijing 100015China Clinical and Research Center of Infectious Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China

Background Studies have reported that low bone mineral density(BMD)is prevalent in human immunodeficiency virus(HIV)-infected patients;however,the factors that contribute to HIV-related BMD changes are yet to be fully understood.Due to the application of dual X-ray absorptiometry(DXA)among a select group of hospitals only,the prevalence and risk factors of low BMD in HIV-infected populations have not been intensively investigated in China.Thus,the aim of our study was to investigate the prevalence of and risk factors associated with BMD changes among antiretroviral therapy(ART)-naive HIV-positive patients in China.Methods The assessment of the prevalence of and risk factors associated with BMD changes was conducted among 156 ART-naive HIV-infected patients.Demographic and clinical data,as well as results of fasting blood tests were obtained from patients.Further,all patients underwent DXA scans to determine BMD,which was then used to classify patients with osteopenia/osteoporosis.The risk factors of reduced BMD were then evaluated using binary logistic regression.Results Among the 156 ART-naive HIV-infected participants,osteopenia and osteoporosis were diagnosed in 48.7%(76/156)and 4.5%(7/156)of patients,respectively.The lumbar spine was most likely to have reduced BMD(49.4%[77/156]),and the proportion of osteopenia in the left hip(32.7%[51/156])was higher than in the right hip(24.4%[38/156]).In the lumbar spine,bone loss rate in the L1 section(60.9%[95/156])was the most significant(L2,53.2%[83/156];L3,45.5%[71/156];L4,52.6%[82/156]).Further analysis showed that,compared with the neck(26.9%[42/156]in the left,18.6%[29/156]in the right)and the interior(15.4%[24/156]in the left,13.5%[21/156]in the right),the trochanter had the greatest probability of reduced BMD(46.2%[72/156]in the left,28.8%[45/156]in the right).In the risk factor analysis,low body mass index(BMI:<18.5 kg/m2)was positively associated with reduced BMD(Exp(B)=39.743,95%confidence interval:3.234-488.399,P=0.004),and was specifically positively correl

关键词： Human immunodeficiency virus(HIV) Antiretroviral therapy-naive Bone mineral density Body mass index

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Next-Generation Sequencing-Based Diagnosis of Bacteremic Listeria monocytogenes Meningitis in a Patient with Anti-Interferon Gamma Autoantibodies:A Case Report

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Infectious Microbes & Diseases 2022年第1期4卷 44-46页

作者： Fanfan Xing Derek L.L.Hung Simon K.F.Lo Shuang Chen Susanna K.P.Lau Patrick C.Y.Woo department of Clinical Microbiology and infection Control The University of Hong Kong–Shenzhen HospitalShenzhenGuangdongChina department of Microbiology The University of Hong KongHong KongChina department of Pathology The University of Hong Kong-Shenzhen HospitalShenzhenGuangdongChina

Although various opportunistic infections have been described in patients with anti-interferon gamma autoantibodies,so far there is no Listeria monocytogenes infection reported to be associated with this primary immunodeficiency.Here,we describe the first case of bacteremic L.monocytogenes meningitis in a 59-year-old Chinese man with anti-interferon gamma autoantibodies,who presented with acute onset of fever and severe headache.Blood culture was positive but culture of the cerebrospinal fluid was negative,although it showed features suggestive of partially treated bacterial meningitis.The presence of L.monocytogenes in the cerebrospinal fluid was confirmed by next-generation sequencing.Avoidance of high-risk food items in these patients is important for the prevention of listeriosis.The use of antibiotic regimens that cover Listeria is crucial for empirical treatment,particularly if such patients develop acute or subacute meningitis.Next-generation sequencing is becoming an important diagnostic modality for culture-negative infections.

关键词： Listeria monocytogenes meningitis anti-interferon gamma autoantibody next-generation sequencing

An Outbreak of infections Caused by a Klebsiella pneumoniae ST11 Clone Coproducing Klebsiella pneumoniae Carbapenemase-2 and RmtB in a Chinese Teaching Hospital

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Chinese Medical Journal 2016年第17期129卷 2033-2039页

作者： Jun Li Ming-Xiang Zou Hai-Chen Wang Qing-Ya Dou Yong-Mei Hu Qun Yan Wen-En Liu department of Clinicat Laboratory Xiangya Hospital Central South University Changsha Hunan 410008 China Department of Infection Control Center Xiangya Hospital Central South University Changsha Hunan 410008 China

Background： Klebsiellapneumoniae carbapenemase （KPC）-producing K. pneumoniae bacteria, which cause serious disease outbreaks worldwide, was rarely detected in Xiangya Hospital, prior to an outbreak that occurred from August 4, 2014, to March 17, 2015. The aim of this study was to analyze the epidemiology and molecular characteristics of the K. pneumoniae strains isolated during the outbreak. Methods： Nonduplicate carbapenem-resistant K. pneumoniae isolates were screened for blanc,＂ and multiple other resistance determinants using polymerase chain reaction. Subsequent studies included pulsed-field gel electrophoresis （PFGE）, multilocus sequence typing, analysis of plasmids, and genetic organization ofblaKPC-2 locus. Results： Seventeen blaKPC-2-positive K. pneumoniae were identified. A wide range of resistant determinants was detected. Most isolates （88.2%） coharbored blaKPC-2 and rmtB in addition to other resistance genes, including biaSHV-1, blaTEM-1, and aac（3）-lla. The blaKPC-2 and rmtB genes were located on the conjugative IncFIB-type plasmid. Genetic organization of blaKPC-2 locus in most strains was consistent with that of the plasmid pKP048. Four types （A l, A2, A3, and B） were detected by PFGE, and Type A1, an ST11, was the predominant PFGE type. A novel K. pneumoniae sequence type （ST1883） related to STI 1 was discovered. Conclusions： These isolates in our study appeared to be clonal and STI 1 K. pneumoniae was the predominant clone attributed to the outbreak. Coharbing of blaKPC-2 and rmtB, which were located on a transferable plasmid, in clinical K. pneumoniae isolates may lead to the emergence of a new pattern of drug resistance.

关键词： Carbapenem： Klebsiella pneumoniae： Klebsiella pneumoniae Carbapenemase Outbreak： RmtB

MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

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Cellular & Molecular Immunology 2022年第2期19卷 234-244页

作者： Yeonsu Kim Xiaoyan Zheng Kathrin Eschke M.Zeeshan Chaudhry Federico Bertoglio Adriana Tomić Astrid Krmpotić Markus Hoffmann Yotam Bar-On Julia Boehme Dunja Bruder Thomas Ebensen Linda Brunotte Stephan Ludwig Martin Messerle Carlos Guzman Ofer Mandelboim Michael Hust Stefan Pöhlmann Stipan Jonjić LukaČičin-Šain department of Viral Immunology Helmholtz Centre for Infection Research(HZI)BraunschweigGermany department of Biotechnology Institut für BiochemieBiotechnologie und BioinformatikTechnischen Universität BraunschweigBraunschweigGermany Oxford Vaccine Group University of OxfordOxfordUK Center for Proteomics University of RijekaFaculty of MedicineRijekaCroatia infection Biology Unit German Primate CenterGöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenGöttingenGermany department of Immunology Rappaport Faculty of MedicineTechnion-Israel Institute of TechnologyHaifaIsrael infection Immunology Institute for Medical Microbiology and Hospital HygieneHealth Campus ImmunologyInfectiology and InflammationOtto-von-Guericke-University MagdeburgMagdeburgGermanyImmune RegulationHelmholtz Centre for Infection ResearchBraunschweigGermany department of Vaccinology and Applied Microbiology Helmholtz Centre for Infection ResearchBraunschweigGermany Institute of Virology Medical University MünsterMünsterGermany Institute of Virology Hannover Medical School(MHH)HannoverGermany German Centre for infection Research(DZIF) Hannover-Braunschweig SiteHannoverGermany Centre for Individualized infection medicine(CiiM) a joint venture of HZI and MHHHannoverGermany

Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality.There remains a medical need for vaccines against these pathogens.CMV(cytomegalovirus)is aβ-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+T cells are maintained for a lifetime.Hence,CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens.We generated two recombinant murine CMV(MCMV)vaccine vectors expressing hemagglutinin(HA)of influenza A virus(MCMV^(HA))or the spike protein of severe acute respiratory syndrome coronavirus 2(MCMV^(S)).A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses,which strengthened over time.Importantly,MCMV^(HA)-vaccinated mice were protected from illness following challenge with the influenza virus,and we excluded that this protection was due to the effects of memory T cells.Conclusively,we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.

关键词： Vaccine vector SARS-CoV-2 Influenza Cytomegalovirus humoral imunity

The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma

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National Science Review 2014年第3期1卷 396-412页

作者： Pengyuan Yang Geoffrey J.Markowitz Xiao-Fan Wang department of Pharmacology and Cancer Biology Duke University Medical Center CAS Key Laboratory of infection and Immunity Institute of Biophysics Chinese Academy of Sciences

In contrast to a majority of cancer types, the initiation of hepatocellular carcinoma(HCC) is intimately associated with a chronically diseased liver tissue, with one of the most prevalent etiological factors being hepatitis B virus(HBV). Transformation of the liver in HBV-associated HCC oten follows from or accompanies long-term symptoms of chronic hepatitis, inlammation and cirrhosis, and viral load is a strong predictor for both incidence and progression of HCC. Besides aiding in transformation, HBV plays a crucial role in modulating the accumulation and activation of both cellular components of the microenvironment,such as immune cells and ibroblasts, and non-cellular components of the microenvironment, such as cytokines and growth factors, markedly inluencing disease progression and prognosis. his review will explore some of these components and mechanisms to demonstrate both underlying themes and the inherent complexity of these interacting systems in the initiation, progression, and metastasis of HBV-positive HCC.

关键词： hepatitis B hepatocellular carcinoma tumor microenvironment leukocytes cytokines growth factors

Expert Recommendation for Novel Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in HIV-Infected Adults

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Infectious Diseases & Immunity 2021年第3期1卷 133-136页

作者： AIDS and Hepatitis C Professional Group,Chinese Society of Infectious Diseases Taisheng Li Hongzhou Lu 不详 department of Infectious Diseases Peking Union Medical College HospitalChinese Academy of Medical Sciences Department of Infection and Immunology Shanghai Public Health Clinical Center

The outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a pandemic.SARS-CoV-2 vaccination is currently being actively promoted worldwide as a promising measure to combat the pandemic.However,human immunodeficiency virus(HIV)-infected individuals who manifest varying degrees of immunodeficiency and chronic inflammation may require special consideration with regards to vaccine types and the timing of immunization depending on specific clinical situations.The present recommendation provides a reference for SARS-CoV-2 vaccination in HIV-infected patients.

关键词： HIV infections Severe acute respiratory syndrome coronavirus 2 Vaccines