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An atlas of immune cell transcriptomes in human immunodeficiency virus-infected immunological non-responders identified marker genes that control viral replication

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Chinese Medical Journal 2023年第22期136卷 2694-2705页

作者： Yahong Chen Xin Li Shuran Liu Wen Ao Jing Lin Zhenting Li Shouli Wu Hanhui Ye Xiao Han Dongliang Li Department of Infection Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouFujian 350025China Department of Infection Fuzong Clinical Medical College of Fujian Medical UniversityFuzhouFujian 362002China College of Biological Science and Engineering Fuzhou UniversityFuzhouFujian 350025China Fujian Provincial Center for Disease Control and Prevention No.76 Jintai RoadFuzhouFujian 350001China department of Hepatobiliary Medicine 900th Hospital of Joint Logistics Support Forces of the Chinese PLAFuzhouFujian 350000China

Background:Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness.This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness.Methods:A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders(IRs)(CD4^(+)T-cell count>500)and immunological non-responders(INRs)(CD4^(+)T-cell count<300)was conducted.The transcriptomic profiles were used to identify distinct cell subpopulations,marker genes,and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness.Results:Among the cellular subpopulations analyzed,the ratios of monocytes,CD16^(+)monocytes,and exhausted B cells demonstrated the most substantial differences between INRs and IRs,with fold changes of 39.79,11.08,and 2.71,respectively.In contrast,the CD4^(+)T cell ratio was significantly decreased(0.39-fold change)in INRs compared with that in IRs.Similarly,the ratios of natural killer cells and terminal effector CD8^(+)T cells were also lower(0.37-fold and 0.27-fold,respectively)in the INRs group.In addition to several well-characterized immune cell-specific markers,we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus(HIV)replication.Notably,ISG15,IFITM3,PLSCR1,HLA-DQB1,CCL3L1,and DDX5,which have been demonstrated to influence HIV replication through their interaction with viral proteins,emerged as significant monocyte marker genes.Furthermore,the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication.Conclusions:We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs.Host genes associated with HIV replication were identified as mark

关键词： Single-cell transcriptome sequencing Human immunodeficiency virus Immunological non-responsiveness CD4 T cell CD8 T cell Natural killer cells HIV replication

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Paneth cells: the hub for sensing and regulating intestinal flora

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Science China(Life Sciences) 2016年第5期59卷 463-467页

作者： Zheng Zhang Zhihua Liu department of Gastroenterology the Affiliated Yixing Hospital of Jiangsu University CAS Key Laboratory of infection and Immunity Institute of Biophysics Chinese Academy of Sciences

The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides in the intestine under steady-state conditions, play a vital role in regulating intestinal flora. Many studies on inflammatory bowel disease(IBD)-associated genes have put Paneth cells at the center of IBD pathogenesis. In this perspective, we focus on mechanistic studies of different cellular processes in Paneth cells that are regulated by various IBD-associated susceptibility genes, and we discuss the hypothesis that Paneth cells function as the central hub for sensing and regulating intestinal flora in the maintenance of intestinal homeostasis.

关键词：细胞分子机理肠道菌群感知宿主免疫肠道内环境 IBD 相互作用共生细菌

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Immunological roulette: Luck or something more? Considering the connections between host and environment in TB

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Cellular & Molecular Immunology 2018年第3期15卷 226-232页

作者： John E Pearl Mrinal Das Andrea M Cooper Department of Infection Immunity and Inflammation Leicester Tuberculosis Research Group(LTBRG)University of LeicesterUniversity RoadLeicesterLE17RHUK

Accurate prediction of which patient will progress from a sub-clinical Mycobacterium tuberculosis infection to active tuberculosis represents an elusive,yet critical,clinical research objective.From the individual perspective,progression can be considered to be the product of a series of unfortunate events or even a run of bad luck.Here,we identify the subtle physiological relationships that can influence the odds of progression to active TB and how this progression may reflect directed dysbiosis in a number of interrelated systems.Most infected individuals who progress to disease have apparently good immune responses,but these responses are,at times,compromised by either local or systemic environmental factors.Obvious disease promoting processes,such as tissue-damaging granulomata,usually manifest in the lung,but illness is systemic.This apparent dichotomy between local and systemic reflects a clear need to define the factors that promote progression to active disease within the context of the body as a physiological whole.We discuss aspects of the host environment that can impact expression of immunity,including the microbiome,glucocorticoid-mediated regulation,catecholamines and interaction between the gut,liver and lung.We suggest the importance of integrating precision medicine into our analyses of experimental outcomes such that apparently conflicting results are not contentious,but rather reflect the impact of these subtle relationships with our environment and microbiota.

关键词： gut-liver-lung axis microbiome tuberculosis

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The microbiota is dispensable for the early stages of peripheral regulatory T cell induction within mesenteric lymph nodes

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Cellular & Molecular Immunology 2021年第5期18卷 1211-1221页

作者： Carolin Wiechers Mangge Zou Eric Galvez Michael Beckstette Maria Ebel Till Strowig Jochen Huehn Joern Pezoldt department Experimental Immunology Helmholtz Centre for Infection ResearchBraunschweigGermany department Microbial Immune Regulation Helmholtz Centre for Infection ResearchBraunschweigGermany department of Computational Biology for Individualised Medicine Centre for Individualised Infection MedicineHelmholtz Centre for Infection Research and Hannover Medical SchoolHannoverGermany Cluster of Excellence RESIST(EXC 2155) Hannover Medical SchoolHannoverGermany Laboratory of Systems Biology and Genetics École Polytechnique Fédérale de LausanneLausanneSwitzerland

Intestinal Foxp3+regulatory T cell(Treg)subsets are crucial players in tolerance to microbiota-derived and food-borne antigens,and compelling evidence suggests that the intestinal microbiota modulates their generation,functional specialization,and maintenance.Selected bacterial species and microbiota-derived metabolites,such as short-chain fatty acids(SCFAs),have been reported to promote Treg homeostasis in the intestinal lamina propria.Furthermore,gut-draining mesenteric lymph nodes(mLNs)are particularly efficient sites for the generation of peripherally induced Tregs(pTregs).Despite this knowledge,the direct role of the microbiota and their metabolites in the early stages of pTreg induction within mLNs is not fully elucidated.Here,using an adoptive transfer-based pTreg induction system,we demonstrate that neither transfer of a dysbiotic microbiota nor dietary SCFA supplementation modulated the pTreg induction capacity of mLNs.Even mice housed under germ-free(GF)conditions displayed equivalent pTreg induction within mLNs.Further molecular characterization of these de novo induced pTregs from mLNs by dissection of their transcriptomes and accessible chromatin regions revealed that the microbiota indeed has a limited impact and does not contribute to the initialization of the Treg-specific epigenetic landscape.Overall,our data suggest that the microbiota is dispensable for the early stages of pTreg induction within mLNs.

关键词： Peripheral regulatory T cells Microbiota Tolerance

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The humoral and cellular immune evasion of SARS-CoV-2 Omicron and sub-lineages

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Virologica Sinica 2022年第6期37卷 786-795页

作者： Tiandan Xiang Junzhong Wang Xin Zheng department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Joint International Laboratory of infection and Immunity Huazhong University of Science and TechnologyWuhan 430022China

The recently discovered SARS-CoV-2 variant Omicron(B.1.1.529) has rapidly become a global public health issue.The substantial mutations in the spike protein in this new variant have raised concerns about its ability to escape from pre-existing immunity established by natural infection or vaccination. In this review, we give a summary of current knowledge concerning the antibody evasion properties of Omicron and its subvariants(BA.2, BA.2.12.1,BA.4/5, and BA.2.75) from therapeutic monoclonal antibodies and the sera of SARS-CoV-2 vaccine recipients or convalescent patients. We also summarize whether vaccine-induced cellular immunity(memory B cell and T cell response) can recognize Omicron specifically. In brief, the Omicron variants demonstrated remarkable antibody evasion, with even more striking antibody escape seen in the Omicron BA.4 and BA.5 sub-lineages. Luckily, the third booster vaccine dose significantly increased the neutralizing antibodies titers, and the vaccine-induced cellular response remains conserved and provides second-line defense against the Omicron.

关键词： SARS-CoV-2 Omicron Vaccine Antibody evasion Cellular immunity

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Genetic diversity and phylogenetic analysis of EG95 sequences of Echinococcus granulosus:Implications for EG95 vaccine application

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Asian Pacific Journal of Tropical Medicine 2017年第5期10卷 497-500页

作者： Wei Pan De-Sheng Chen Yun-Juan Lu Hui-Wen Xu Wen-Ting Hao Ya-Wen Zhang Su-Ping Qin Kui-Yang Zheng Ren-Xian Tang Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyLaboratory of Infection and ImmunityXuzhou Medical University department of Clinical Medicine Xuzhou Medical University

Objective:To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus(E. granulosus). Methods:We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1(DNASTAR Inc.,Madison,WI),and the phylogenetic analysis was performed by using MEGA5.1(CEMI,Tempe,AZ,USA). In addition,linear and conformational epitopes were analysed,including secondary structure,NXT/S glycosylation,fibronectin type ecoⅢ(Fnndary Ⅲ) domain and glycosylphosphatidylinositol anchor signal(GPIanchor). The s structure was predicted by PSIPRED method. Results:Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence,X90928. However,EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates,respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine,X90928,and they belonged to Subgroup 1. However,in comparison to X90928,several amino acid mutations occurred in most isolates besides oncosphere,which potentially altered the immunodominant linear epitopes,glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. Conclusions:This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates,and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.

关键词： Echinococcus granulosus Cystic echinococcosis EG95 Vaccine Genetic diversity

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Glycolytic Shunts Replenish the Calvin-Benson-Bassham Cycle as Anaplerotic Reactions in Cyanobacteria

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Molecular Plant 2020年第3期13卷 471-482页

作者： Alexander Makowka Lars Nichelmann Dennis Schulze Katharina Spengler Christoph Wittmann Karl Forchhammer Kirstin Gutekunst department of Biology Botanical InstituteUniversity Kiel24118 KielGermany Institute for Systems Biotechnology Saarland University66123 SaarbruckenGermany Organismic Interactions department Interfaculty Institute for Microbiology and Infection MedicineUniversity

The recent discovery of the Entner-Doudoroff(ED)pathway as a third glycolytic route beside Embden-Meyerhof-Parnas(EMP)and oxidative pentose phosphate(OPP)pathway in oxygenic photoautotrophs requires a revision of their central carbohydrate metabolism.In this study,unexpectedly,we observed that deletion of the ED pathway alone,and even more pronounced in combination with other glycolytic routes,diminished photoautotrophic growth in continuous light in the cyanobacterium Synechocystis sp.PCC 6803.Furthermore,we found that the ED pathway is required for optimal glycogen catabolism in parallel to an operating Calvin-Benson-Bassham(CBB)cycle.It is counter-intuitive that glycolytic routes,which are a reverse to the CBB cycle and do not provide any additional biosynthetic intermediates,are important under photoautotrophic conditions.However,observations on the ability to reactivate an arrested CBB cycle revealed that they form glycolytic shunts that tap the cellular carbohydrate reservoir to replenish the cycle.Taken together,our results suggest that the classical view of the CBB cycle as an autocatalytic,completely autonomous cycle that exclusively relies on its own enzymes and C02 fixation to regenerate ribulose-1,5-bisphosphate for Rubisco is an oversimplification.We propose that in common with other known autocatalytic cycles,the CBB cycle likewise relies on anaplerotic reactions to compensate for the depletion of intermediates,particularly in transition states and under fluctuating light conditions that are common in nature.

关键词： central carbohydrate metabolism Calvin-Benson-Bassham cycle Entner-Doudoroff pathway oxidative pentose phosphate pathway Embden-Meyerhof-Parnas pathway cyanobacteria

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Relationship between cytokines gene polymorphism and susceptibility to hepatitis B virus intrauterine infection

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Chinese Medical Journal 2005年第19期118卷 1604-1609页

作者： ZHU Qi-rong GE Yan-ling GU Shao-qing YU Hui WANG Jian-she GU Xin-huan FEI Lin-e DONG Zuo-quan Department of Infection Disease Children＇s Hospital FudanUniversity Shanghai 200032 China

Background The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines （tumor necrosis factor-α, interferon-γ, interleukin-4 and interleukin-10）, which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism （SNP） and susceptibility to hepatitis B virus intrauterine infection. Methods This is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus （HBV） intrauterine infection were divided into immune failure group （group Ⅰ） ; and immune effective group （group Ⅱ） and non high risk children belonged to the control group. Four gene SNP sites of TNF-α -238, IFN-γ ＋874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction （PCR）. Results The significant differences of TNF-α- 238 A allele frequency were found between group Ⅰand group Ⅱ（X^2 =6. 797, P 〈 0.05 ） and between group Ⅰ and the control group （ X^2 = 9. 513, P 〈 0.05 ）. No evident differences of TNF-α- 238 A were found between group Ⅱand control group （ X^2 = 0. 047, P 〉 0. 05 ） ; the significant differences of IFN-γ ＋ 874 A allele frequency were found between group Ⅰand group Ⅱ（ X^2 = 7. 238, P〈0. 05）, and between group Ⅰand the control group （X^2 =5. 199,P 〈0. 05）. No evident differences were found between groupⅡ and the control group （ X^2 =0. 602 ,P 〉0. 05 ） ; the significant differences of IL-4 -590 C/T allele frequency were not found between groupⅠand group Ⅱ （ X^2 = 0. 632, P 〉 0. 05 ） , also group Ⅰ and the control group （ x^2 = 0. 584, P 〉 0. 05

关键词： cytokine gene polymorphism hepatitis B virus infection uterus susceptibility

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Follicular helper T cells in immune homeostasis

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Cellular & Molecular Immunology 2012年第5期9卷 367-368页

作者： Dr X Yang Laboratory for infection and Immunity Department of Medical Microbiology Faculty of Medicine University of Manitoba Winnipeg Manitoba Canada

Cellular ＆ Molecular Immunology（2012） 9, 367-368; doi：10.lO38/cmi.2012.27; published online 7 September 2012In recent years, follicular helper T （TFH） cells have become a hot topic for immunologists due to their... 详细信息

关键词：内环境稳定康奈尔医学指数变态反应和免疫学

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Contribution of Quick Sequential Organ Failure Assessment Score Combined with Electrocardiography in Risk Stratification of Patients with Acute Pulmonary Embolism

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Chinese Medical Journal 2018年第20期131卷 2395-2401页

作者： Fei Teng Yun-Xia Chen Xin-Hua He Shu-Bin Guo department of Emergency Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China Department of Infection and Microbiology Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China

Background： The quick Sequential Organ Failure Assessment （qSOFA） score emerged recently. We investigated its contribution to risk stratification in acute pulmonary embolism （PE） by combining with electrocardiography （ECG）. Methods： Acute PE patients diagnosed in Beijing Chao-Yang Hospital, Capital Medical University, from 2008 to 2018 were retrospectively studied and divided into high- and low-risk groups by imaging and biomarkers. The ECG scores consisted oftachycardia, McGinn-White sign （S1Q3T3）, right bundle branch block, and T-wave inversion of leads V1-V3. A new combination of qSOFA scores and ECG scores by logistic regression for predicting high-risk stratification patients with acute PE was evaluated by a receiver operating characteristic curve. Results： Totally 1318 patients were enrolled, including 271 in the high-risk group and 1047 in the low-risk group. A combination predictive scoring system named qSOFA-ECG = qSOFA score ＋ ECG score was created. The optimal cutoffvalue for qSOFA-ECG was 2, and the sensitivity, specificity, positive predictive value, and negative predictive value were 81.5%, 72.3%, 43.2%, and 93.8%, respectively. For predicting high-risk stratification and reperfusion therapy, the qSOFA-ECG is superior to PE Severity Index （PESI） and simplified PESI. Conclusions： The qSOFA score contributes to identify acute PE patients with potentially hemodynamic decompensation that need monitoring and possible reperfusion therapy at the emergency department arrival when used in combination with ECG score.

关键词： Electrocardiography Emergency Pulmonary Embolism Quick Sequential Organ Failure Assessment

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