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Hydroxyapatite nanoparticles drive the potency of Toll-like receptor 9 agonist for amplified innate and adaptive immune response

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Nano Research 2022年第10期15卷 9286-9297页

作者： Qin Zeng Ruiqi Wang Yuchen Hua Hongfeng Wu Xuening Chen You-cai Xiao Qiang Ao Xiangdong Zhu Xingdong Zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterials&Institute of Regulatory Science for Medical Devices&NMPA Research Base of Regulatory Science for Medical Devices Sichuan UniversityChengdu 610064China College of Biomedical Engineering Sichuan UniversityChengdu 610064China Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan UniversityChengdu 610041China

The potency of Toll-like receptor 9(TLR9)agonist to drive innate immune response was limited due to immune suppression or tolerance during TLR9 signaling activation in immune *** we addressed this problem by introducing hydroxyapatite nanoparticles(HANPs)to CpG ODN(CpG),a TLR9 *** study revealed that HANPs concentration and durationdependently reprogramed the immune response by enhancing the secretion of immunostimulatory cytokines(tumor necrosis factorα(TNFα)or IL-6)while reducing the production of immunosuppressive cytokine(IL-10)in macrophages in response to ***,the enhanced immune response benefited from increased intracellular Ca2+in macrophage by the addition of ***,we found exposure to HANPs impacted the mitochondrial function of macrophages in support of the synthesis of adenosine triphosphate(ATP),the production of nicotinamide adenine dinucleotide(NAD),and reactive oxygen species(ROS)in the presence or absence of *** vaccinated mice model,only one vaccination with a mixture of CpG,HANPs,and OVA,a model antigen,allowed the development of a long-lasting balanced humoral immunity in mice without any histopathological change in the local injection ***,this study revealed that HANPs could modulate the intracellular calcium level,mitochondrial function,and immune response in immune cells,and suggested a potential combination adjuvant of HANPs and TLR9 agonist for vaccine development.

关键词： hydroxyapatite nanoparticles Toll-like receptor 9 intracellular calcium mitochondrial function adaptive immune response

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Impact of adaptive immune response and cellular infection on delayed virus dynamics with multi-stages of infected cells

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International Journal of Biomathematics 2020年第1期13卷 79-140页

作者： A.M.Elaiw N.H.AlShamrani Department of Mathematics Faculty of Science King Abdulaziz UniversityP.O.Box 80203 Jeddah 21589Saudi Arabia Department of Mathematics Faculty of Science University of JeddahP.O.Box 80327 Jeddah 21589Saudi Arabia

In this investigation,we propose and analyze a virus dynamics model with multi-stages of infected *** model incorporates the effect of both humoral and cell-mediated immune *** consider two modes of transmissions,virus-to-cell and *** intracellular discrete-time delays have been integrated into the *** incidence rate of infection as well as the generation and removal rates of all compartments are described by general nonlinear *** derive five threshold parameters which determine the existence of the equilibria of the model under consideration.A set of conditions on the general functions has been established which is sufficient to investigate the global stability of the five equilibria of the *** global asymptotic stability of all equilibria is proven by utilizing Lyapunov function and LaSalle’s invariance *** theoretical results are illustrated by numerical simulations of the model with specific forms of the general functions.

关键词： Viral and cellular infections global stability adaptive immune response Lyapunov function multi-staged infected cells.

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Dynamic analysis of a latent HIV infection model with CTL immune and antibody responses

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International Journal of Biomathematics 2024年第3期17卷 289-316页

作者： Zhiqi Zhang Yuming Chen Xia Wang Libin Rong School of Mathematics and Statistics Xinyang Normal University XinyangHenan 464000P.R.China Department of Mathematics Wilfrid Laurier University WaterlooONN2L 3C5Canada Department of Mathematics University of Florida GainesvilleFL 32611USA

This paper develops a mathematical model to investigate the Human Immunodeficiency Virus(HIV)infection *** model includes two transmission modes(cell-to-cell and cell-free),two adaptive immune responses(cytotoxic T-lymphocyte(CTL)and antibody),a saturated CTL immune response,and latent HIV *** existence and local stability of equilibria are fully characterized by four reproduction *** sensitivity analyses,we assess the partial rank correlation coefficients of these reproduction numbers and identify that the infection rate via cell-to-cell transmission,the number of new viruses produced by each infected cell during its life cycle,the clearance rate of free virions,and immune parameters have the greatest impact on the reproduction ***,we compare the effects of immune stimulation and cell-to-cell spread on the model's *** findings highlight the significance of adaptive immune responses in increasing the population of uninfected cells and reducing the numbers of latent cells,infected cells,and ***,cell-to-cell transmission is identified as a facilitator of HIV *** analytical and numerical results presented in this study contribute to a better understanding of HIV dynamics and can potentially aid in improving HIV management strategies.

关键词： HIV infection cell-to-cell transmission adaptive immune response latent infection local stability

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Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

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Cellular & Molecular Immunology 2015年第3期12卷 273-282页

作者： Zhiyong Ma Ejuan Zhang Dongliang Yang Mengji Lu Institute of Virology University Hospital Essen University of Duisburg-Essen Essen Germany Department of Infectious Diseases Zhongnan Hospital ofWuhan University Wuhan China Wuhan Institute of Virology Chinese Academy of Sciences Wuhan China Department of Infectious Diseases Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus （HBV） infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors （TLRs） sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons （IFNs） and pro-inflammatory cytokines. Experimental results from in vitroand in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T- and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

关键词： Hepatitis B virus Toll like receptor Innate immune response adaptive immune response

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Innate and adaptive immune responses correlate with Peginterferon alfa treatment efficacy in chronic hepatitis B patients(the OSST Immunology study)

Innate and adaptive immune responses correlate with Peginter...

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第九届全国免疫学学术大会

作者： Weiming Yan Di Wu Xiaojing Wang Tao Chen Qintao Lai Qi Zheng Jiaji Jiang Jinlin Hou Meifang Han Qin Ning Department and Institute of Infectious Disease Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Hepatology Unit and Department of Infectious Diseases Nanfang HospitalSouthern Medical University Department of Liver Diseases Research Center First Affiliated Hospital of Fujian Medical University

Objective:The aim of this study was to characterize the immunological features responsible for improved treatment responses in 77 patients with chronic hepatitis B(CHB)treated with peginterferon(Peg IFN)alfa-2a after switching them from entecavir(ETV)***:Peripheral natural killer(NK)cells,Toll-like receptors(TLRs),T cells,regulatory T cells(Tregs)and programmed death 1(PD-1)were evaluated dynamically by flow *** was defined as hepatitis B e antigen(HBeAg)seroconversion,hepatitis B surface antigen(HBsAg)loss,and HBsAg seroconversion(either as singular events or in combination at week 48)Results:From week 12 to week 24,compared with ETV responders or Peg IFN alfa non-responders,Peg IFN alfa responded exhibited a significant decline in Treg proportions as well as a diminished negative regulation of CD8+T cells by *** HBeAg-negative patients at baseline treated with Peg IFN alfa also showed significantly decreased Treg proportions and a higher rate of HBsAg ***,Peg IFN alfa responders showed a significantly higher increase in the NKG2C+NK cell proportions from baseline to week 12 and of TLR2+monocytes at week 12 than Peg IFN alfa *** Successful response to Peg IFN alfa correlates with an early significant restoration of impaired immune *** antiviral treatment response can be achieved by both IFN and ETV,the underlying immunological features vary which may explain the generally observed difference in off-treatment durability of response between the two treatments,as well as effects on HBsAg.

关键词： Innate immune response adaptive immune response Peginterferon alfa Entecavir Chronic Hepatitis B

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MAP Kinases in immune responses

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Cellular & Molecular Immunology 2005年第1期2卷 20-27页

作者： YongliangZhang ChenDong DepartmentofImmunology MDAndersonCancerCenterUniversityofTexas.HoustonTX77030.USA DepartmentofImmunology MDAndersonCancerCenterUniversityofTexas.HoustonTX77030.USA／／Correspondingto：Dr.ChenDongDepartmentofImmunology.MDAndersonCancerCenterHoustonTexas77030USA

MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune *** are three main families of MAPKs in *** of them has its own activators,inactivators,substrates and scaffolds,which altogether form a fine signaling network in response to different extracellular or intracellular *** this review,we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune *** & Molecular Immunology.2005;2(1):20-27.

关键词： MAP kinase MAP kinase phosphatase scaffold protein innate immune response adaptive immune response

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A key role for PTP1B in dendritic cell maturation, migration, and T cell activation

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分子细胞生物学报:英文版 2015年第6期7卷 517-528页

作者： Cristina Martin-Granados Alan R.Prescott Samantha Le Sommer Izabela P.Klaska Tian Yu Elizabeth Muckersie Claudiu V.Giuraniuc Louise Grant Mirela Delibegovic John V.Forrester Institute of Medical Sciences University of AberdeenCollege of Life Sciences and MedicineAberdeen AB252ZDUK Department of Pharmacology University of CambridgeCambridge CB21PDUK Division of Cell Biology and Immunology College of Life SciencesUniversity of DundeeDundee DD15EHUK Centre for Ophthalmology and Visual Science The University of Western AustraliaPerthAustralia Centre for Experimental Immunology Lions Eye InstituteNedlandsWA 6009Australia

Dendritic cells(DC)are the major antigen-presenting cells bridging innate and adaptive immunity,a function they perform by converting quiescent DC to active,mature DC with the capacity to activate naı¨ve T *** do this by migrating from the tissues to the T cell area of the secondary lymphoid ***,wedemonstrate thatmyeloid cell-specific genetic deletion of PTP1B(LysM PTP1B)leads to defects in lipopolysaccharide-driven bone marrow-derivedDC(BMDC)activation associated with increased levels of phosphorylated *** showthatmyeloid cell-specific PTP1Bdeletion also causes decreased migratory capacity of epidermal DC,aswell as reduced CCR7 expression and chemotaxis to CCL19 by ***1B deficiency in BMDC also impairs their migration in ***,immature LysM PTP1B BMDC display fewer podosomes,increased levels of phosphorylated Src at tyrosine 527,and loss of Src localization to podosome *** co-culture with T cells,LysM PTP1B BMDC establish fewer and shorter contacts than control ***,LysMPTP1BBMDCfail to present antigen to T cells as efficiently as *** data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.

关键词： dendritic cell maturation podosomes T cell activation adaptive immune response protein tyrosine phosphatase 1B

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COVID-19 and gut immunomodulation

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World Journal of Gastroenterology 2021年第46期27卷 7925-7942页

作者： Koushik Roy Sidra Agarwal Rajib Banerjee Manash K Paul Prabhat K Purbey Microbiology and Immunology Department of PathologySchool of MedicineUniversity of UtahSalt Lake CityUT 84112United States Department of Gastroenterology Shadan Institute of Medical SciencesPeeramcheru 500086TelanganaIndia Department of Electronics and Communication Engineering Dr.B.C.Roy Engineering CollegeDurgapur 713206West BengalIndia Division of Pulmonary and Critical Care Medicine David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA 90095United States Department of Microbiology Immunology and Molecular GeneticsUniversity of California Los AngelesLos AngelesCA 90095United States

The disease coronavirus disease 2019(COVID-19)is a severe respiratory illness that has emerged as a devastating health problem *** disease outcome is heterogeneous,and severity is likely dependent on the immunity of infected individuals and *** symptoms of the disease are primarily associated with respiratory problems,additional infection or failure of other vital organs are being *** reports suggest a quite common co-existence of gastrointestinal(GI)tract symptoms in addition to respiratory symptoms in many COVID-19 patients,and some patients show just the GI *** possible cause of the GI symptoms could be due to direct infection of the epithelial cells of the gut,which is supported by the fact that(1)The intestinal epithelium expresses a high level of angiotensin-converting enzyme-2 and transmembrane protease serine 2 protein that are required for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into the cells;(2)About half of the severe COVID-19 patients show viral RNA in their feces and various parts of the GI tract;and(3)SARS-CoV-2 can directly infect gut epithelial cells in vitro(gut epithelial cells and organoids)and in vivo(rhesus monkey).The GI tract seems to be a site of active innate and adaptive immune responses to SARS-CoV-2 as clinically,stool samples of COVID-19 patients possess proinflammatory cytokines(interleukin 8),calprotectin(neutrophils activity),and immunoglobulin A *** addition to direct immune activation by the virus,impairment of GI epithelium integrity can evoke immune response under the influence of systemic cytokines,hypoxia,and changes in gut microbiota(dysbiosis)due to infection of the respiratory system,which is confirmed by the observation that not all of the GI symptomatic patients are viral RNA *** review comprehensively summarizes the possible GI immunomodulation by SARS-CoV-2 that could lead to GI symptoms,their association with disease sev

关键词： COVID-19 Gastrointestinal symptoms Pathogenesis Innate immune response adaptive immune response Gut microbiota Dysbiosis Therapeutics Probiotic Pre-existing diseases

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Impact of SARS-CoV-2 on neuropsychiatric disorders

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World Journal of Psychiatry 2021年第7期11卷 347-354页

作者： Maria Angeles Robinson-Agramonte Carlos-Alberto Goncalves Elena Noris-García NaybíPréndes Rivero Anna Lisa Brigida Stephen Schultz Dario Siniscalco Ramiro Jorge García García Neuroimmunology Department Research CenterInternational Center for Neurological RestorationHavana 11300Cuba Department of Biochemistry Federal University of Rio Grande do SulPorto Alegre 90040-060Brazil Immunology Department National Institute of NephrologyHavana 10600Cuba Department of Mental Health San Antonio de los Baños HospitalHavana 38100Cuba Department of Mental and Physical Health and Preventive Medicine University of CampaniaNaples 80138Italy Department of Cellular and Integrative Physiology School of MedicineUniversity of Texas Health San AntonioSan AntonioTX 78229United States Department of Experimental Medicine University of CampaniaNaples 80138Italy Children Hospital“Juan Manuel Márquez” Havana 11500Cuba

Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019(COVID-19)from early disease *** most frequent symptoms and signs are fatigue,dizziness,impaired consciousness,ageusia,anosmia,radicular pain,and headache,as well as *** on the high number of series of cases reported,there is evidence for the implication of the immune system in the pathological mechanism of *** the exact role of the immunological mechanism is not elucidated,two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and *** the context of neurological manifestations associated with COVID-19,neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression,anxiety,mood alterations,psychosis,post-traumatic stress disorder,delirium,and cognitive impairment,which appear to be common in COVID-19 survivors.A worsened score on psychopathological measures is seen in those with a history of psychiatric *** review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.

关键词： COVID-19 Immunological mechanism Neuropsychiatric manifestation Cytokine storm adaptive immune response Innate immune response

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Interactions between the lung microbiome and host immunity in chronic obstructive pulmonary disease

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Chronic Diseases and Translational Medicine 2023年第2期9卷 104-121页

作者： Yixing Zhu De Chang Graduate School of The PLA General Hospital BeijingChina Department of Respiratory and Critical Care Medicine Eighth Medical CenterDepartment of Respiratory and Critical Care Seventh Medical CenterChinese PLA General HospitalBeijingChina

Chronic obstructive pulmonary disease(COPD)is a common chronic respiratory disease and the third leading cause of death *** in next-generation sequencing technology have improved microbiome analysis,which is increasingly recognized as an important component of disease *** to the gut,the lung is a biosphere containing billions of microbial *** lung microbiome plays an important role in regulating and maintaining the host immune *** microbiome composition,metabolites of microorganisms,and the interactions between the lung microbiome and the host immunity profoundly affect the occurrence,development,treatment,and prognosis of *** this review,we drew comparisons between the lung microbiome of healthy individuals and that of patients with ***,we summarize the intrinsic interactions between the host and the overall lung microbiome,focusing on the underlying mechanisms linking the microbiome to the host innate and adaptive immune response ***,we discuss the possibility of using the microbiome as a biomarker to determine the stage and prognosis of COPD and the feasibility of developing a novel,safe,and effective therapeutic target.

关键词： adaptive immune response chronic obstructive pulmonary disease innate immune response microbiome

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