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Exploring the modulatory role of bovine lactoferrin on the microbiome and the immune response in healthy and Shiga toxin‑producing E.coli challenged weaned piglets

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1278-1291页

作者： Matthias Dierick Ruben Ongena Daisy Vanrompay Bert Devriendt Eric Cox Laboratory of Immunology Department of Translational PhysiologyInfectiology and Public HealthFaculty of Veterinary MedicineGhent UniversitySalisburylaan 1339820 MerelbekeBelgium Laboratory for Immunology and Animal Biotechnology Faculty of Bioscience EngineeringGhent UniversityCoupure links 6539000 GhentBelgium

Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.

关键词： E.coli immune modulation Lactoferrin Microbiome

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Probiotics intervention in colorectal cancer:From traditional approaches to novel strategies

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Chinese Medical Journal 2024年第1期137卷 8-20页

作者： Suki Ha Xiang Zhang Jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status.These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis,metabolism,and immune response.The disruption of microbiota,known as dysbiosis,has been implicated in many intestinal diseases,including colorectal cancer(CRC).As the third most common cancer and the second leading cause of cancer-related death worldwide,CRC poses a significant health burden.There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes.Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment.Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC,alleviating treatment-related side effects,and potentiating the efficacy of anticancer therapy,which is the key to successful translation to clinical practice.This paper aims to review the traditional probiotics and new interventions,such as next-generation probiotics and postbiotics,in the context of CRC.The underlying mechanisms of probiotic anti-cancer effects are also discussed,including the restoration of microbial composition,reinforcement of gut barrier integrity,induction of cancer cell apoptosis,inactivation of carcinogens,and modulation of host immune response.This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy.Despite all the promising findings presented in studies,the evaluation of potential risks,optimization of delivery methods,and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

关键词： colorectal cancer probiotics gut microbiota dysbiosis adjuvant therapy immune modulation gut barrrier

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Meningeal lymphatic vasculature,a general target for glioblastoma therapy?

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Fundamental Research 2024年第2期4卷 267-269页

作者： Changping Zhou Han Xu Jincai Luo Laboratory of Vascular Biology Institute of Molecular MedicineCollege of Future TechnologyBeijing Key Laboratory of Cardiometabolic Molecular MedicinePeking UniversityBeijing 100871China

Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical studies.The central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this notion.MLVs are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph nodes.In the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including GBM.Here,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.

关键词： Meningeal lymphatic vessels Glioblastoma Immunity Vascular endothelial growth factor C immune modulation

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Engineering white blood cell membrane-camouflaged nanocarriers for inflammation-related therapeutics

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Bioactive Materials 2023年第5期23卷 80-100页

作者： Wanli Song Pengfei Jia Yaping Ren Junmiao Xue Bingqian Zhou Xinkai Xu Yansheng Shan Jing Deng Qihui Zhou Department of Stomatology Institute for Translational MedicineThe Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao266003China Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang 325000China Dental Biomaterials Technology Innovation Center of Qingdao Qingdao266003ShandongChina School of Stomatology Qingdao UniversityQingdao266003China Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid Tianjin300038China School of Rehabilitation Sciences and Engineering University of Health and Rehabilitation SciencesQingdao266071China

White blood cells(WBCs)play essential roles against inflammatory disorders,bacterial infections,and cancers.Inspired by nature,WBC membrane-camouflaged nanocarriers(WBC-NCs)have been developed to mimic the“dynamic”functions of WBCs,such as transendothelial migration,adhesion to injured blood vessels,etc,which make them promising for diverse medical applications.WBC-NCs inherit the cell membrane antigens of WBCs,while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent(bio)physicochemical performance.This review summarizes the proposed concept of cell membrane engineering,which utilizes physical engineering,chemical modification,and biological functionalization technologies to endow the natural cell membrane with abundant functionalities.In addition,it highlights the recent progress and applications of WBC-NCs for inflammation targeting,biological neutralization,and immune modulation.Finally,the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.

关键词： White blood cell membrane-camouflaged nanocarriers Inflammation targeting Biological neutralization immune modulation

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Tricking the tumour microenvironment into becoming our best rational drug design factory:reversal of immune suppression

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 615-623页

作者： Martin L.Ashdown Faculty of Medicine Dentistry and Health SciencesUniversity of MelbourneMelbourne 3011Australia

The immune cellular components of the tumour microenvironment are a diverse group of cells that paradoxically are now appreciated to have a coordinated opposing duality of either promoting or retarding tumour growth.Manipulating this seemingly dynamic interaction for therapeutic benefit is a hotbed of much research.Recent findings in tumour immunology(both preclinical and clinical)build on more than a century of insights and provide a way forward to improving patient outcomes,long term survival and the predictability of“cures”.This opinion piece attempts to summarise some of these historical and contemporary insights with a view to describing eminently testable therapeutic solutions.

关键词： Tumour microenvironments immune suppression regulatory T cells immune modulation reversal plasticity spatio-temporal

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Lobe-specific modulation of B16MET melanoma lung metastases by nephrilin peptide

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 239-245页

作者： Desmond D.Mascarenhas Puja Ravikumar Edward P.Amento Mayflower Organization for Research&Education SunnyvaleCA 94085USA Transporin Inc.SunnyvaleCA 94085USA Molecular Medicine Research Institute SunnyvaleCA 94085USA

Aim:Nephrilin peptide modulates systemic immune responses to trauma in contexts characterized by simultaneous inflammation and immunosuppression.This study explores the possibility that nephrilin peptide may modulate lung metastasis,which also occurs in an environment of concurrent inflammation and immunosuppression.Methods:B16MET melanoma cells were injected via the tail vein of mice and the development of lung metastases was recorded in animals treated with nephrilin peptide or vehicle by subcutaneous bolus injection daily for three weeks.In a separate experiment,nephrilin was administered by subcutaneous bolus injection for seven days to study the biodistribution of peptide and possible changes to plasma cytokine levels.Results:Nephrilin significantly suppressed B16MET lung metastases.Suppression was more effective in deep lobes with the poorest access to circulation:accessory>inferior>middle>superior.In a separate biodistribution study in mice,nephrilin showed similar biodistribution levels in kidney,liver,brain,and left lung,but significantly higher accumulation in the lobes of the right lung in a gradient that matched its effectiveness in suppressing metastases(accessory>inferior>middle).The latter environments were also characterized by significantly higher local concentrations of succinate,a proxy for lower levels of oxygenation.Conclusion:Nephrilin accumulates preferentially in the deep lobes of the right lung in mice and inhibits B16MET right lung metastases in a lobe-specific manner.

关键词： Nephrilin melanoma metastases deep lung lobes anoxia oxidative stress immune modulation

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immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum

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Protein & Cell 2013年第3期4卷 197-210页

作者： Qi Sun Xi Chen Jianxiong Yu Ke Zen Chen-Yu Zhang Liang Li Jiangsu Engineering Research Center for microRNA Biology and Biotechnology State Key Laboratory of Pharmaceutical BiotechnologyNanjing University School of Life SciencesNanjing 210093China Department of Virology University of California School of Public HealthBerkeleyCA 94720USA

Colostrum provides essential nutrients and immunologically active factors that are beneficial to newborns.Our previous work demonstrated that milk contains large amounts of miRNA that is largely stored in milk-derived microvesicles(MVs).In the present study,we found that the MVs from colostrum contain signifi cantly higher levels of several immune-related miRNAs.We hypothesized that the colostrum MVs may transfer the immune-related miR-NAs into cells,which contribute to its immune modulatory feature.We isolated colostrum MVs by ultracentrifugation and demonstrated several immune modulation features associated with miRNAs.We also provide evidence that the physical structure of milk-derived MVs is essential for transfer miRNAs and following immune modulation effect.Moreover,we found that colostrum powder-derived MVs also contains higher levels of immune-related miRNAs that display similar immune modulation effects.Taken together,these results show that MV-containing immunerelated miRNAs may be a novel mechanism by which co-lostrum modulates body immune response.

关键词： colostrum miRNAs microvesicles immune modulation

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Effective intrahepatic CD8＋ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes

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Cellular & Molecular Immunology 2016年第6期13卷 805-815页

作者： Aaron Ochel Marcin Cebula Mathias Riehn Upneet Hillebrand Christoph Lipps Reinhold Schirmbeck Hansjorg Hauser Dagmar Wirth Model Systems for Infection and Immunity Helmholtz Centre for Infection Research Inhoffenstr. 7 38124 Braunschweig Germany Clinic for Internal Medicine I University Hospital UIm Albert-Einstein-Allee 23 89081 UIm Germany Experimental Hematology Medical School Hannover Carl-Neuberg-Str. 1 D-30625 Hannover Germany Current address Institute for Immunology Justus-Liebig University Giessen BFS Schubertstr. 81 35390 Giessen Germany

Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8＋ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8＋ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin （Ova） as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.

关键词： antigen load chronicity immune modulation T-cell exhaustion

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Effects of Sodium Copper Chlorophyllin on Mesenchymal Stem Cell Function in Aplastic Anemia Mice

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Chinese Journal of Integrative Medicine 2013年第5期19卷 360-366页

作者：尹利明蒋慧芳王潇钱煦岱高瑞兰林筱洁陈小红王灵聪 Research Institute of Hematopathy the First Affiliated HospitalZhejiang Chinese Medical University Tongde Hospital of Zhejiang Province

Objective： To investigate the effects of sodium copper chlorophyllin （SCC） on the proliferation, differentiation and immunomodulatory function of mesenchymal stem cells （MSCs） from mice with aplastic anemia. Methods： A mouse model of aplastic anemia was established by exposure of BALB/c mice to sublethal doses of 5.0 Gy Co60 γ radiation, followed by transplantation of 2 × 108 lymph node cells from DBA/2 donor mice within 4 h after radiation. Aplastic anemic BALB/c mice were randomly divided into six groups： the treated groups, which received 25, 50, or 100 mg/kg/day SCC, respectively; a positive control group treated with cyclosporine A （CsA）; and an untreated model control group （model group）; while, the non-irradiated mice as the normal control group. SCC or CsA were administered by gastrogavage for 20 days, starting on day 4 after irradiation. Peripheral blood cells were counted and colony-forming fibroblasts （CFU-F） in the bone marrow were assayed. The ability of MSCs to form calcium nodes after culture in osteoinductive medium was also observed. The immunosuppressive effect of MSCs on T lymphocytes was analyzed by enzyme-linked immunosorbent assay and flow cytometry, to evaluate the efficacy of SCC in mice with aplastic anemia. Results： Peripheral blood white cell and platelet counts were increased by medium and high SCC doses, compared with the untreated control. CFU-Fs were also increased compared with the untreated control, and the numbers of calcium nodes in MSCs in osteoinductive medium were elevated in response to SCC treatment. The percentage of Forkhead box protein 3 （FOXP3^＋） T cells was increased in T celI-MSC cocultures, and the cytokine transforming growth factor 131 was up-regulated in SCC-treated groups. Conclusion： The results of this study suggest that SCC not only promotes the proliferation and differentiation of MSCs, but also improves their immunoregulatory capacity in mice with apiastic anemia.

关键词： sodium copper chlorophyllin mesenchymal stem cell proliferation differentiation immune modulation

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Radiotherapy as an immune checkpoint blockade combination strategy for hepatocellular carcinoma

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World Journal of Gastroenterology 2021年第10期27卷 919-927页

作者： Byung Min Lee Jinsil Seong Department of Radiation Oncology Yonsei Cancer CenterYonsei University College of MedicineSeoul 03722South Korea

In the immune oncology era,the clinical efficacy of immune checkpoint inhibitors(ICIs)against most solid cancers is well known.In hepatocellular carcinoma,the recent success of combination therapy with targeting agents has accelerated the search for novel combination strategies.Radiotherapy(RT),an attractive modality,can be combined with ICIs,which act as strong modulators of the tumor immune microenvironment.Herein,we discuss immune modulation caused by radiation and the current trials of RT-ICI combination treatment as well as future perspectives.

关键词： Hepatocellular carcinoma immune checkpoint inhibitor Radiotherapy immune modulation Tumor microenvironment immune oncology

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