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PI4P STimulatING innate immune activation:beyond the Golgi

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Cellular & Molecular Immunology 2023年第12期20卷 1399-1400页

作者： Yi Zheng Xuejing Zhang Chengjiang Gao Key Laboratory of infection and Immunity of Shandong Province Department of ImmunologySchool of Basic Medical SciencesShandong UniversityJinan250012ShandongChina

The cGAS–STING pathway is pivotal for sensing cytosolic DNA[2].cGAS,a cytoplasmic DNA sensor,can be stimulated by DNA,and it consumes ATP and GTP to synthesize a second messenger,2'3'-cGAMP,which binds to STING,resulting in STING conformational change,oligomerization,and activation;ultimately,this process leads to the production of cytokines such as type I interferon to mediate antiviral and antitumor immune responses(Fig.1).Phosphoinositides,derived from phosphatidylinositol(PI),are phospholipids in membranes and are also crucial signaling molecules[3].The D-3,D-4,or D-5 positions in the inositol head group can be phosphorylated;therefore,a total of seven different PIP molecules exist in *** 4-phosphate(PI4P)is distributed in various membrane components,with the highest amount in the trans-Golgi network(TGN)[4].The PI4P level in cells is regulated by its PI4K synthetases(PI4KA,PI4KB,PI4K2A,and PI4K2B)and the lipid phosphatase *** addition to being a precursor for PIP2 and PIP3,PI4P is a crucial signaling molecule involved in vesicular transport,lipid transport,and organelle morphology maintenance.

关键词： activation positions synthesize

Regulatory B cells in autoimmune diseases

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Cellular & Molecular Immunology 2013年第2期10卷 122-132页

作者： Min Yang Ke Rui Shengjun Wang Liwei Lu department of Pathology and Center for infection and Immunology The University of Hong Kong Hong Kong China department of Immunology School of Medical Science and Laboratory Medicine Jiangsu University Zhenjiang China These authors contributed equally to this work.

B cells are generally considered to be positive regulators of the immune response because of their capability to produce antibodies, including autoantibodies. The production of antibodies facilitates optimal CD4＋ T-cell activation because B cells serve as antigen-presenting cells and exert other modulatory functions in immune responses. However, certain B cells can also negatively regulate the immune response by producing regulatory cytokines and directly interacting with pathogenic T cells via cell-to-cell contact. These types of B Cells are defined as regulatory B （Breg） cells. The regulatory function of Breg cells has been demonstrated in mouse models of inflammation, cancer, transplantation, and particularly in autoimmunity. In this review, we focus on the recent advances that lead to the understanding of the development and function of Breg cells and the implications of B cells in human autoimmune diseases.

关键词： autoimmune disease interleukin-lO regulatory B cells

Structural immunology of costimualtory and coinhibitory molecules

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Science China(Life Sciences) 2010年第2期53卷 183-189页

作者： WANG ShengDian1 & CHEN LiePing1,2 1Center for infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China 2department of Oncology,Johns Hopkins University School of Medicine,Baltimore,Maryland,USA Center for infection and Immunity Institute of Biophysics Chinese Academy of Sciences Beijing China department of Oncology Johns Hopkins University School of Medicine Baltimore USA

The T cell costimulatory pathways are central to regulating immune responses,and targeting these pathways represents one of the most promising approaches for achieving *** molecular structures of costimulation revealed invaluable mechanistic insights underlying costimulatory receptor/ligand specificity,affinity,oligomeric state,and valency,which provided the bases for better manipulation of these signaling *** incredible growth of this field led to identification of new members and unexpected interactions,revealing a complicated regulatory network of immune *** advances in structural biology of costimulation will promise unprecedented opportunities for furthering our understanding and therapeutic application of T cell costimulatory pathways.

关键词： costimulatory molecules T cells molecular structure immunotherapy

Outlook on the gut microbiota

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Gastroenterology Report 2022年第1期10卷 1-2页

作者： Bjoern O.Schroeder department of Molecular Biology UmeaUniversityUmeaSweden Laboratory for Molecular infection Medicine Sweden(MIMS) UmeaUniversityUmeaSweden

Despite being a rather young research field that only emerged in the last two decades,it has become clear that the gut microbiota is an essential part of our body that strongly influences the processes that regulate our health and *** this Special Issue of Gastroenterology Report,we have compiled a collection of articles which discuss that microbial signals deriving from our internal bioreactor are by no means restricted to the gut environment,and why it is thus reasonable to consider the gut microbial community as an additional organ to our body.

关键词： Outlook spite restricted

In vitro-in vivo studies on anti-trypanosomal potentials of Zapoteca portoricensis

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Asian Pacific Journal of Tropical Medicine 2009年第1期2卷 25-29页

作者： Nwodo NJ Omeje EO Bran R department of Pharmaceutical Chemistry University of NigeriaNsukkaNigeria department of Medical Parasitology and infection Biology Swiss Tropical InstituteCH-4002 BaselSwitzerland

Objective:Aqueous extracts of Zapoteca portoricensis are used traditionally as antidiarrhea agent and in the treatment of diverse gastrointestinal disorders here in Nigeria specifically,the southern ***,the aqueous extract of the plant is also used traditionally as anticonvulsant,antispasmodic and in the treatment of *** too,the anti-inflammatory and antimicrobial activities of the methanol extracts of the root of Zapoteca portoricensis was *** this research,we are set to investigate the trypanocidal activity of Zapoteca ***:The methanol extract of the root of Zapoteca portoricensis was investigated for both in vitro and in vivo trypanocidal activity following established *** summary,phytochemical analysis was carried out on both the crude powdered root and on the methanol extract following standard procedures. The oral acute toxicity test(LD50 ) of the crude methanol extract was determined according to the method described by Lorke（1983）.Albino mice（17g-21g） of either sex were *** methanol extract was suspended in 3%v/v tween 85 and administered orally at doses of 10 mg/kg,100 mg/kg and 1 000 mg/kg to three groups of mice（n = 3 ）.The animals were observed for 24 *** on the result obtained in this initial test,doses of 4 mg/kg,6 mg/kg,and 8 mg/kg were administered to three different *** LD50 was calculated as the geometric mean of the lowest dose killing a mouse and the highest dose showing no *** invivo /in-vitro antitrypanosomal evaluations were carried out in experimental animals and tissue cell culture respectively. Results:The result of the in vitro studies shows the inhibitive concentration-50（IC-50） against Trypanosoma brucei rhodesiense（***） to be 0.372 mg/kg,while the control drug melarsoprol was 0.006 mg/*** Trypanosoma brucei brucei（***）,the IC-50 is 6.42 mg/kg against 0.87 of the reference drug *** cytotoxicity on L-6 c

关键词： Zapoteca portoricensis Trypanocidal effects T.b.rhodensiense T.cruzi In vitro/in vivo model

Correlation between Saccharomyces cerevisiae DNA in intestinal mucosal samples and anti-Saccharomyces cerevisiae antibodies in serum of patients with IBD

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World Journal of Gastroenterology 2006年第2期12卷 292-297页

作者： RC Mallant-Hent M Mooij BME von Blomberg RK Linskens AA van Bodegraven PHM Savelkoul department of Gastroenterology VU University Medical CenterAmsterdamThe Netherlands department of Medical Microbiology and infection Control VU University Medical CenterAmsterdamThe Netherlands department of Immunology VU University Medical CenterAmsterdamThe Netherlands department of Gastroenterology St Anna ZiekenhuisGeldropThe Netherlands

AIM： To investigate the correlation between ASCA and presence of mucosal S. cerevisiae DNA in a population of CD, ulcerative colitis （UC） patients and controls. METHODS： S. cerevisiae-specific primers and a fluorescent probe were designed for a 5＇ exonuclease real time PCR （TaqManTM） assay, which is a homogenous system using a fluorescent-labelled probe for the detection of PCR product in real time. We analyzed the relation of the PCR results with the ASCA findings in a group of 76 inflammatory bowel disease （IBD） patients （31 CD, 45 UC） and 22 healthy controls （HC）. RESULTS： ASCA （IgA or IgG） were positive in 19 （61%） patients with CD, 12 （27%） with UC and none of the HC. PCR amplification was inhibited and excluded from the final results in 10 （22%） UC patients, 7 （22%） CD patients, and 6 （30%） HC. In only 15 of the mucosal samples, S. cerevisiae DNA was detected by real time PCR, including 7 （29%） in CD, 7 （19%） in UC, 1 （6%） in HC. In 4 CD and in 4 UC patients, ASCA and mucosal S. cerevisiae were positive. Hucosal S. cerevisiae was present in combination with negative ASCA IgA and IgG in 3 UC, and 3 CD patients. CONCLUSION： We conclude that since the presence of S. cerevisiae in colonic mucosal biopsy specimens is very rare, ASCA is unlikely to be explained by continuous exposure to S. cerevisiae in the mucosa. Therefore, ASCA formation must occur earlier in life and levels remain relatively stable thereafter in immunological susceptible persons.

关键词： ASCA Saccharomyces cerevisiae mucosa IBD

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)

Immune formulation-assisted conventional therapy on anti-infective effectness of multidrug-resistant Mycobacterium tuberculosis infection mice

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Asian Pacific Journal of Tropical Medicine 2016年第3期9卷 288-292页

作者： Xiu-Li Yuan Qiang Wen Ming-De Ni Li-Kun Wang Internal Medicine department No.3 Eastern Medical District of Linyi People's Hospital infection department.Eastern Medical District of Linyi People's Hospital

Objective:To study the effect of immune formulation-assisted conventional therapy on antiinfective ability of multidrug-resistant Mycobacterium tuberculous infection ***:BALB/c mice were used as experimental animals,multidrug-resistant Mycobacterium tuberculosis infection models were built,randomly divided into model group,moxifloxacin group,thymopentin group and combined treatment group and given corresponding drug intervention,and then colony numbers in the spleen and lung,T lymphocyte subset contents and programmed death-1(PD-1) expression levels in peripheral blood were ***:Colony numbers in lung and spleen of moxifloxacin group and thymopentin group were significantly lower than those of model group and colony numbers in lung and spleen of combined treatment group were significantly lower than those of moxifloxacin group and thymopentin group:contents of CD3^+CD4^+T cells,Thl and Thl7 in peripheral blood of moxifloxacin group and thymopentin group were higher than dtose of model group,and contents of CD3^+CD8^+T ***2 and Treg were lower than those of model group;contents of CD3^+CD4^+T *** 1 and Th 17 in peripheral blood of combined treatment group were higher than those of moxifloxacin group and thymopentin group,and contents of CD3^+CD8^+T ***2 and Treg were lower than those of moxifloxacin group and thymopentin group:PD-I expression levels on T lymphocyte,B lymphocyte and monocyte surface in peripheral blood of moxifloxacin group and thymopentin group were lower than those of model group,and PD-I expression levels on T lymphocyte.B lymphocyte and monocyte surface in peripheral blood of combined treatment group were lower than those of moxifloxacin group and thymopentin ***:Immune formulation thymopentin can enhance the anti-infective ability of multidrug-resistant Mycobacterium tuberculosis infection mice,decrease bacterial load in lung and spleen,and enhance immune function.

关键词： Mycobacterium tuberculosis Multidrug resistance Thymopentin Immune function

Toxoplasma gondii and human immunodeficiency virus co-infection in western Iran: A cross sectional study

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Asian Pacific Journal of Tropical Medicine 2018年第1期11卷 58-62页

作者： Naser Nazari Arezoo Bozorgomid Alireza Janbakhsh Farshid Bashiri department of Medical Parasitology and Mycology Faculty of Medicine Kermanshah University of Medical Sciences department of Microbiolgy Asadabad School of Medical Sciences department of infection Disease Faculty of Medicine Kermanshah University of Medical Sciences

Objective: To determine Toxoplasma gondii(T. gondii) as a cause of morbidity and mortality in human immunodeficiency virus(HIV) infected patients by ELISA method and to investigate toxoplasmosis-associated risk factors. Methods: This cross sectional study was conducted with 385 patients with HIV/AIDS referred to the behavior disease consultation center in Kermanshah, Iran between May 2012 and June 2013. Anti-Toxoplasma IgG and IgM antibodies were measured by using the ELISA method. Also, the relationship between the infection and age, gender, education, occupation, antiretroviral status, CD4+ cell counts and some other factors of the patients were assessed. Pinfections with the age group(Pinfection were at the high risk of developing toxoplasmosis disease especially those patients who do not receive antiretroviral therapy and prophylaxis. The development and use of the effectiveness-based guidelines for controlling and the prevention reactivation of the latent T. gondii infection is required.

关键词： Seroepidemiology Toxoplasmosis HIV Iran