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Unveiling the Threat: Case Reports of Extra-Pulmonary Tuberculosis among Sanctuary Chimpanzees

Advances in Infectious Diseases 2024年第1期14卷 105-132页

作者： Emeline Chanove Yedra Feltrer Antoine Collomb-Clerc Angela Ceballos-Caro Marina Spinu Department of Infectious Diseases University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca Romania international Primate Health and Welfare Group (IPHWG) Madrid Spain NeuroX institute and Brain Mind institute School of Life Sciences Swiss Federal Institute of Technology (EPFL) Lausanne Switzerland Malaria and Emerging Parasitic Diseases Laboratory National Centre for Microbiology Instituto de Salud Carlos III Madrid Spain

Primate sanctuaries across Africa play a pivotal role in the rescue and rehabilitation of confiscated and rescued wild primates, many of whom have had extensive contact with humans prior to their arrival and throughout the rehabilitation process, heightening the risk of disease transmission. While tuberculosis is not naturally occurring in free-living chimpanzees, it has been extensively observed in captive primates that have been in close proximity to humans or other captive primates infected with Mycobacterium tuberculosis. This case report delves into an outbreak of extra-pulmonary tuberculosis among juvenile chimpanzees within a sanctuary, detailing the associated diagnostic challenges and treatment approaches. The five cases had close contact with a caregiver infected with tuberculosis, subsequently transmitting the infection to other in-contact chimpanzees. Prolonged treatment, employing the human protocol of quadri-therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol), followed by bi-therapy (rifampicin and isoniazid), resulted in complete resolution for all five cases. These cases underscore the critical importance of maintaining high levels of biosecurity, implementing effective quarantine measures, and adhering to strict hygiene practices when working with non-human primates.

关键词： Extrapulmonary Tuberculosis Tuberculosis Chimpanzees Zoonotic Risk Biosecurity Diagnosis Challenges

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Innate and adaptive T cells in influenza disease

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Frontiers of Medicine 2018年第1期12卷 34-47页

作者： Simone Nfissing Sneha Sant Marios Koutsakos Kanta Subbarao Thi H.O. Nguyen Katherine Kedzierska Department of Microbiology and Immunology University of Melbourne at the Peter Doherty Institute for Infection and Immunity Parkville 3010 Victoria Australia World Health Organisation (WHO) Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity Melbourne 3000 Victoria Australia

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza- specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses （T cells and antibody-producing B cells） achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T- cells （MAIT cells, y~ T cells, and NKT cells） in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and γδ T cells as well as adaptive CD8＋ and CD4＋ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

关键词： influenza innate T cells CD4＋ and CD8＋ T cells vaccination

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Molecular Mechanisms of Lymphocyte-Mediated Cytotoxicity

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Cellular & Molecular Immunology 2005年第4期2卷 259-264页

作者： Zusen Fan Qixiang Zhang National Laboratory of Biomacromolecules Center for Infection and Immunity Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China

Granule-mediated cytotoxicity is the major mechanism for lymphocytes to kill viruses, intracellular bacteria and tumors. The cytotoxic granules move to the immunological synapse by exocytosis after recognition of a killer cell. The contents of the granules are delivered into target cells with the help of perforin by endocytosis. A group of serine protease granzymes cleave their critical substrates to initiate DNA damage and cell death. The most abundant granzymes are granzyme A and B. They induce cell death through alternate and nonoverlapping pathways. The substrates and functions of the majority of the orphan granzymes have not yet been identified. It is possible that the diversity of granzymes provides fail-safe mechanisms for killing viruses and tumor cells.

关键词： CTL NK granule cytotoxicity mechanism apoptosis

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Complementary Presence of HBV Humoral and T-cell Response Provides Protective immunity after Neonatal Immunization

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Journal of Clinical and Translational Hepatology 2022年第4期10卷 660-668页

作者： Yunmei Huang Yuting Yang Tingting Wu Zhiyu Li Hongmei Xu Ailong Huang Yao Zhao National Clinical Research Center for Child Health and Disorders China International Science and Technology Cooperation base of Child development and Critical DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Infection and ImmunityChildren’s Hospital of Chongqing Medical UniversityChongqingChina Department of infection Children’s Hospital of Chongqing Medical UniversityChongqingChina institute for Viral Hepatitis Ministry of Education Key Laboratory of Molecular Biology on Infectious DiseasesChongqing Medical UniversityChongqingChina

Background and Aims:Hepatitis B vaccination is the most cost effective way to prevent hepatitis B virus(HBV)infection.Hepatitis B vaccine(HepB)efficacy is usually assessed by an-ti-hepatitis B surface antigen(HBsAg)level,but there are few reports of humoral and cellular immune responses to HepB in children after neonatal vaccination.Methods:A group of 100 children with a history of primary hepatitis B immunization were included in this study to evaluate the efficacy of HepB.Blood samples were obtained from 80 children before,and 41 children after,a single HepB booster dose.Children with low anti-HBsAg(HBs)titers of<100 mIU/mL received a booster dose after giving their informed consent.Anti-HBsAg,T-cell re-sponse and percentage of B-cell subsets were assayed before and after the booster.Results:Of the 80 children,81.36%had positive T cell and anti-HBsAg responses at baseline.After the booster dose,the anti-HBsAg titer(p<0.0001),positive HBsAg-specific T-cell response(p=0.0036),and spot-form-ing cells(p=0.0003)increased significantly.Compared with pre-existing anti-HBsAg titer<10 mIU/mL,the anti-HBsAg(p=0.0005)and HBsAg-specific T-cell responses(p<0.0001)increased significantly in preexisting anti-HBsAg titer between 10 and 100 mIU/mL group.Change of the HBV-specific hu-moral response was the reverse of the T-cell response with age.Peripheral blood lymphocytes,B cells,and subset fre-quency decreased.Conclusions:HBV immunization protec-tion persisted at least 13 years after primary immunization because of the complementary presence of HBV-specific hu-moral antibodies and a T-cell immune response.One dose of a HepB booster induced protective anti-HBsAg and promoted an HBsAg-specific T-cell response.In HBV endemic regions,a HepB booster is recommended to children without anti-HBsAg because of effectiveness in HBV prevention.

关键词： Hepatitis B virus Hepatitis B vaccine Booster Children

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Plasmacytoid dendritic cells in antiviral immunity and autoimmunity

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Science China(Life Sciences) 2010年第2期53卷 172-182页

作者： TANG Fei1,2,DU Qiumei1,2 & LIU Yong-Jun3 1 Center for infection and immunity,institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China 2 Graduate University of Chinese Academy of Sciences,Beijing 100049,China 3 Department of Immunology and Center for Cancer Immunology Research,University of Texas,M.D.Anderson Cancer Center,Houston,Texas 77030,USA Center for infection and immunity Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China.

Plasmacytoid dendritic cells (pDCs) represent a unique and crucial immune cell population capable of producing large amounts of type I interferons (IFNs) in response to viral infection.The function of pDCs as the professional type I IFN-producing cells is linked to their selective expression of Toll-like receptor 7 (TLR7) and TLR9,which sense viral nucleic acids within the endosomal compartments.Type I IFNs produced by pDCs not only directly inhibit viral replication but also play an essential role in linking the innate and adaptive immune system.The aberrant activation of pDCs by self nucleic acids through TLR signaling and the ongoing production of type I IFNs do occur in some autoimmune diseases.Therefore,pDC may serve as an attractive target for therapeutic manipulations of the immune system to treat viral infectious diseases and autoimmune diseases.

关键词： plasmacytoid dendritic cells type I interferon TLR7 TLR9 antiviral immunity autoimmune diseases

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The TNFα/TNFR2 axis mediates natural killer cell proliferation by promoting aerobic glycolysis

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Cellular & Molecular Immunology 2023年第10期20卷 1140-1155页

作者： Abrar Ul Haq Khan Alaa Kassim Ali Bryan Marr Donghyeon Jo Simin Ahmadvand Claire Fong-McMaster Saeedah Musaed Almutairi Lisheng Wang Subash Sad Mary-Ellen Harper Seung-Hwan Lee Department of Biochemistry Microbiologyand ImmunologyFaculty of MedicineUniversity of OttawaOttawaONCanada The University of Ottawa Centre for infection Immunityand InflammationOttawaONCanada Botany and Microbiology Department College of SciencesKing Saud UniversityRiyadhSaudi Arabia

Natural killer(NK)cells are predominant innate lymphocytes that initiate the early immune response during infection.NK cells undergo a metabolic switch to fuel augmented proliferation and activation following infection.Tumor necrosis factor-alpha(TNFα)is a well-known inflammatory cytokine that enhances NK cell function;however,the mechanism underlying NK cell proliferation in response to TNFαis not well established.Here,we demonstrated that upon infection/inflammation,NK cells upregulate the expression of TNF receptor 2(TNFR2),which is associated with increased proliferation,metabolic activity,and effector function.Notably,IL-18 can induce TNFR2 expression in NK cells,augmenting their sensitivity toward TNFα.Mechanistically,TNFα-TNFR2 signaling upregulates the expression of CD25(IL-2Rα)and nutrient transporters in NK cells,leading to a metabolic switch toward aerobic glycolysis.Transcriptomic analysis revealed significantly reduced expression levels of genes involved in cellular metabolism and proliferation in NK cells from TNFR2 KO mice.Accordingly,our data affirmed that genetic ablation of TNFR2 curtails CD25 upregulation and TNFα-induced glycolysis,leading to impaired NK cell proliferation and antiviral function during MCMV infection in vivo.Collectively,our results delineate the crucial role of the TNFα-TNFR2 axis in NK cell proliferation,glycolysis,and effector function.

关键词： Natural killer cells TNFa TNFR2 Glycolysis Proliferation Murine cytomegalovirus

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Transcriptome analysis reveals immune-related genes in tissues of Vibrio anguillarum-infected turbot Scophthalmus maximus

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Journal of Oceanology and Limnology 2024年第1期42卷 332-344页

作者： Yuting SONG Maqsood Ahmed SOOMRO Xianzhi DONG Guobin HU College of Marine Life Sciences Ocean University of ChinaQingdao 266003China institute of Evolution&Marine Biodiversity Ocean University of ChinaQingdao 266003China institute of Biophysis Chinese Academy of SciencesBeijing 100101China

Turbot Scophthalmus maximus is an important mariculture fish species with high economic value.However,the bacterial diseases caused by Vibrio anguillarum infection bring huge economic losses to the turbot aquaculture industry.To understand the immune response of the turbot against V.anguillarum infection and to explore novel immune-related genes,the transcriptome analysis of turbot spleen and gills were conducted after V.anguillarum infection.Differentially expressed genes(DEGs)were identified in spleen and gill of the turbot amounted to 17261 and 16436,respectively.A large number of immunerelated DEGs were enriched in cytokine-cytokine receptor interaction signaling pathway,and the others by the kyoto encyclopedia of genes and genomes(KEGG)enrichment.The gene ontology(GO)classification analysis revealed that V.anguillarum infection had the greatest effect on biological processes and cellular components.Twelve immune-related DEGs were identified in the spleen(cstl.1,egfl6,lamb21,v2rx4,calcr,and gpr78a)and gills(ghra,sh3gl2a,cst12,inhbaa,cxcl8,and il-1b)by heat map.The proteinprotein interaction(PPI)networks were constructed to analyze the immune mechanism.The results demonstrate that the maturation and antigen processing of major histocompatibility complex(MHC)class II molecule,and calcitonin-or adrenomedullin-regulated physiological activity were important events in the immunity of turbot against V.anguillarum infection.In the gills,the protein interactions in TGF-βsignaling pathway,production of inflammatory factors,and endocytosis regulation were most significant.Our research laid a foundation for discovering novel immune-related genes and enriching the knowledge of immune mechanisms of turbot against V.anguillarum infection.

关键词： Scophthalmus maximus Vibrio anguillarum transcriptome differentially expressed genes immune mechanism

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Impact of vaccination on the dynamics of COVID-19:A mathematical study using fractional derivatives

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international Journal of Biomathematics 2024年第2期17卷 201-232页

作者： Shraddha Ramdas Bandekar Mini Ghosh C.Rajivganthi Division of Mathematics School of Advanced Sciences Vellore Institute of TechnologyChennaiIndia

Arrival of a new disease marks a yearlong destruction of human lives and economy in general,and if the disease turns out to be a pandemic the loss is frightening.COVID-19 is one such pandemic that has claimed millions of lives till date.There is a suffering throughout the world due to various factors associated with the pandemic,be it loss of livelihoods because of sudden shutdown of companies and lockdown,or loss of lives due to lack of medical aid and inadequate vaccination supplies.In this study,we develop a six-compartmental epidemiological model incorporating vaccination.The motivation behind the study is to analyze the significance of higher vaccination efficacy and higher rate of population getting vaccinated in controlling the rise in infectives and thereby the untimely demise of various individuals.The work begins with an ordinary differential equation model followed by stability analysis of the same,after which a fractional-order derivative model of the same is formulated and the existence of uniformly stable solution for the system is proved.In addition to this,we present the stability of the equilibria in general for the fractional model framed.The sensitivity analysis of the basic reproduction number along with its correlation with various parameters is presented.In addition to this,sensitivity of certain state variables in the fractional model with respect to different.fractional orders as well with respect to different infection rate is exhibited in this work.Factors related to lockdown and usage of face shields are incorporated in the entire study,and importance of these is highlighted in the study as well.The major takeaway from the study is that mere vaccination will not sufice in eradication of the virus.The vaccine efficacy plays a major role along with other intervention included in the model.The numerical simulations are carried out in MATLAB software using ode45 and fdel2.

关键词： Caputo fractional derivative basic reproduction number stability analysis sensitivityanalysis vaccination

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The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy

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Cellular & Molecular Immunology 2015年第6期12卷 656-668页

作者： Mateusz Legut David K Cole Andrew K Sewell Division of infection and immunity and Svstems Immunitv Universitv Research institute. Cardiff University School of Medicine Cardiff UK

γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of humanγδT cell receptors （TCRs） remain largely unknown, but recent studies have confirmed the recognition of phosphorylated prenyl metabolites, lipids in complex with CD1 molecules and markers of cellular stress. All of these molecules are upregulated on various cancer types, highlighting the potential importance of the γδ T cell compartment in cancer immunosurveiliance and paving the way for the use of γδTCRs in cancer therapy. Ligand recognition by the γδ TCR often requires accessorylco-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. Unlike αβ T cells, γδ T cells recognise their targets irrespective of HLA haplotype and therefore offer exciting possibilities for off-the-shelf, pan-population cancer immunotherapies. Here, we present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment.

关键词： cancer γδ T cells immunotherapy phosphoantigens T cell receptor

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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

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