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Signal Transduction and Targeted Therapy 2022年第11期7卷 3973-3975页

作者： Ivan Odak Reinhold Förster Berislav Bošnjak Institute of Immunology Hannover Medical School30625HannoverGermany cluster of excellence resist(EXC 2155) Hannover Medical School30625HannoverGermany German Centre for Infection Research(DZIF) Partner site HannoverHannoverGermany

Sokal et *** recently in Immunity that the SARS-CoV-2 Omicron variant evades recognition by 70%of anti-spike protein antibodies generated by memory B cells(MBCs)from mRNA vaccine-immunized individuals that were either or not also infected with ***,samples from all analyzed persons contained MBCs with neutralizing antibodies against Omicron Spike receptor-binding domain(RBD),which provide protection against this SARS-CoV-2 variant to some degree.

关键词： vaccine antibodies

NK cell dysfunction in severe COVID-19:TGF-β-induced downregulation of integrin beta-2 restricts NK cell cytotoxicity

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Signal Transduction and Targeted Therapy 2022年第2期7卷 346-348页

作者： Joana Barros-Martins Reinhold Förster Berislav Bošnjak Institute of Immunology Hannover Medical School30625 HannoverGermany cluster of excellence resist(EXC 2155) Hannover Medical School30625 HannoverGermany German Centre for Infection Research(DZIF) Partner site HannoverHannoverGermany

In a recent study published in Nature,Witkowski et *** that in patients with severe forms of coronavirus disease 2019(COVID-19)deranged tumor growth factor-beta(TGF-β)secretion counteracts interferon-alpha(IFN-α)-induced activation of NK cells by decreasing expression of transcription factor ***,NK cells fail to upregulate the adhesion molecule integrin beta-2(-ß2),which impedes their attachment to and killing of SARS-CoV-2 infected cells.

关键词： interferon cytotoxicity

Cellular and molecular mechanisms breaking immune tolerance in inborn errors of immunity

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Cellular & Molecular Immunology 2021年第5期18卷 1122-1140页

作者： Georgios Sogkas Faranaz Atschekzei Ignatius Ryan Adriawan Natalia Dubrowinskaja Torsten Witte Reinhold Ernst Schmidt Department of Rheumatology and Immunology Hannover Medical SchoolHanoverGermany Hannover Medical School Cluster of Excellence RESIST(EXC 2155)HanoverGermany

In addition to susceptibility to infections,conventional primary immunodeficiency disorders(PIDs)and inborn errors of immunity(IEI)can cause immune dysregulation,manifesting as lymphoproliferative and/or autoimmune *** can be the prominent phenotype of PIDs and commonly includes cytopenias and rheumatological diseases,such as arthritis,systemic lupus erythematosus(SLE),and Sjogren’s syndrome(SjS).Recent advances in understanding the genetic basis of systemic autoimmune diseases and PIDs suggest an at least partially shared genetic background and therefore common pathogenic ***,we explore the interconnected pathogenic pathways of autoimmunity and primary immunodeficiency,highlighting the mechanisms breaking the different layers of immune tolerance to self-antigens in selected IEI.

关键词： Inborn errors of immunity Primary immunodeficiencies Autoimmunity Rheumatic diseases

Differential retention of lymph-borne CD8 memory T cell subsets in the subcapsular sinus of resting and inflamed lymph nodes

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Cellular & Molecular Immunology 2021年第5期18卷 1317-1319页

作者： Ginka Nikolova Siegfried Weiss Berislav Bosnjak Reinhold Förster Institute of Immunology Hannover Medical School30625HannoverGermany cluster of excellence resist(EXC 2155) Hannover Medical School30625HannoverGermany

Immunological memory represents the ability of specific immune cells to recall an encounter with a cognate *** results in an immediate response upon a second exposure to the same infectious ***,conventional memory T cells are generated after encountering specific foreign *** contrast,a group of innate memory T cells develops without initial exposure to foreign antigen that specifically binds to a cognate T cell receptor.1 These naturally occurring memory-like T cells,also known as“virtual”memory T cells,are generated under steady-state *** accumulate during aging in both humans and mice.2 By comparing the TCR repertoire of young and old mice,an early study identified age-dependent clonal expansion and age-related changes in CD8^(+) but not CD4^(+) T cells.3 Interestingly,more than 50%of CD62L^(hi)CD44^(hi) central memory T cells in the peripheral blood of aged naive mice have been suggested to represent virtual memory T cells based on their lower expression levels of CD49d.4 Infection studies in mice employing Listeria monocytogenes showed that both virtual memory T cells and conventional antigen-specific memory T cells were able to provide protection.5 However,in contrast to virtual memory T cells,conventional memory T cells produced fivefold higher levels of IFN-γupon short-term in vitro TCR stimulation.

关键词： lymph retention exposure

Efficient IL-2R signaling differentially affects the stability,function,and composition of the regulatory T-cell pool

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Cellular & Molecular Immunology 2021年第2期18卷 398-414页

作者： Marc Permanyer Berislav Bošnjak Silke Glage Michaela Friedrichsen Stefan Floess Jochen Huehn Gwendolyn E.Patzer Ivan Odak Nadine Eckert Razieh Zargari Laura Ospina-Quintero Hristo Georgiev Reinhold Förster Institute of Immunology Hannover Medical SchoolHannoverGermany Institute for Laboratory Animal Science Hannover Medical SchoolHannoverGermany Department Experimental Immunology Helmholtz Centre for Infection ResearchBraunschweigGermany cluster of excellence resist(EXC 2155) Hannover Medical School30625HannoverGermany

Signaling via interleukin-2 receptor(IL-2R)is a requisite for regulatory T(Treg)cell identity and ***,it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis,lineage stability and function in both resting and inflammatory ***,we characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25,theα-chain of IL-2R,which resulted in diminished receptor expression and reduced IL-2R *** noninflammatory conditions,Cd25Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune *** contrast,Cd25^(Y^(129H))Treg cells failed to efficiently induce immune suppression and lost lineage commitment in a T-cell transfer colitis model,indicating that unimpaired IL-2R signaling is critical for Treg cell function in inflammatory ***,single-cell RNA sequencing of Treg cells revealed that impaired IL-2R signaling profoundly affected the balance of central and effector Treg cell ***,partial loss of IL-2R signaling differentially interferes with the maintenance,heterogeneity,and suppressive function of the Treg cell pool.

关键词： Regulatory T cells IL-2R signaling scRNA sequencing Treg heterogeneity

Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks

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Signal Transduction and Targeted Therapy 2022年第1期7卷 243-257页

作者： Louisa Ruhl Isabell Pink Jenny F.Kiihne Kerstin Beushausen Jana Keil Stella Christoph Andrea Sauer Lennart Boblitz Julius Schmidt Sascha David Hans-Martin Jack Edith Roth Markus Cornberg Thomas F.Schulz Tobias Welte Marius M.Hoper Christine S.Falk Institute of Transplant Immunology MHHDHanoverGermany Department of Pneumology MHHDHanoverGermany Department of Intensive Care Medicine University of ZurichCHZurichSwitzerland Division of Molecular Immunology Internal Medicine IIINikolaus-Fiebiger-Center of Molecular MedicineFriedrich-Alexander University Erlangen-NurnbergDErlangenGermany Department of Gastroenterology Hepatology and Endocrinology MHHDHanoverGermany Center for Individualized Infection Medicine CiiM HanoverGermany lnstitute of Virology MHHDHanoverGermany German Center for Infection Research DZIFTTU-IICHMarburgGermany excellence cluster 2155 resist MHHHanoverGermany German Center for Lung Diseases DZL/BREATH MarburgGermany

The systemic processes involved in the manifestation of life・threatening COVID-19 and in disease recovery are still incompletely understood,despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 *** define hallmarks of severe COVID-19 in acute disease(n=58)and in disease recovery in con valesce nt patie nts(n=28)from Han nover Medical School,we used flow cytometry and proteomics data with unsupervised clustering *** our observational study,we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and *** patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific *** core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe *** within this sign ature were associated with either disease progression or *** summary,our data suggest that besides a strong inflammatory response,severe COVID-19 is driven by endothelial activation and barrier disruption,whereby recovery depends on the regeneration of the endothelial integrity.

关键词： cytokine networks signature

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 *** bacterial species and microbiota-derived metabolites,such as short-chain fatty acids(SCFAs),have been reported to promote Treg homeostasis in the intestinal lamina ***,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 ***,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 *** mice housed under germ-free(GF)conditions displayed equivalent pTreg induction within *** 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 ***,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

Neutralization of the SARS-CoV-2 Delta variant after heterologous and homologous BNT162b2 or ChAdOx1 nCoV-19 vaccination

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Cellular & Molecular Immunology 2021年第10期18卷 2455-2456页

作者： Swantje I.Hammerschmidt Berislav Bosnjak Günter Bernhardt Michaela Friedrichsen Inga Ravens Alexandra Dopfer-Jablonka Markus Hoffmann Stefan Pöhlmann Georg M.N.Behrens Reinhold Förster Institute of Immunology Hannover Medical SchoolHannoverGermany Department for Rheumatology and Immunology Hannover Medical SchoolHannoverGermany Infection Biology Unit German Primate Center-Leibniz Institute for Primate ResearchGöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenGöttingenGermany German Center for Infection Research(DZIF) Partner Site Hannover-BraunschweigHannoverGermany German Center for Lung Research(DZL) HannoverGermany cluster of excellence resist(EXC 2155) Hannover Medical SchoolHannoverGermany

Since the beginning of the COVID-19 pandemic,divergent variants of concern(VoCs)of SARS-CoV-2 have evolved and become the most prevalent SARS-CoV-2 variants in distinct locations at different ***,the Delta variant(B.1.617.2)dominates infection events in large parts of the *** campaigns,however,still use SARS-CoV-2 vaccines based on the spike(S)protein of the original Wuhan virus.

关键词： Delta homologous campaign

Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods

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Cellular & Molecular Immunology 2021年第4期18卷 936-944页

作者： Berislav Bosnjak Saskia Catherina Stein Stefanie Willenzon Anne Katrin Cordes Wolfram Puppe Gunter Bernhardt Inga Ravens Christiane Ritter Christian R.Schultze-Florey Nina Godecke Jorg Martens Hannah Kleine-Weber Markus Hoffmann Anne Cossmann Mustafa Yilmaz Isabelle Pink Marius M.Hoeper Georg M.N.Behrens Stefan Pohlm ann Rainer Blasczyk Thomas F.Schulz Reinhold Forster Institute of Immunology Hannover Medical SchoolHannoverGermany lnstitute of Virology Hannover Medical SchoolHannoverGermany Department of Hematology HemostasisOncology and Stem Cell TransplantationHannover Medical SchoolHannoverGermany Institute of Transfusion Medicine and Transplant Engineering Hannover Medical SchoolHannoverGermany German Primate Center-Leibniz Institute for Primate Research GottingenGermany Faculty of Biology and Psychology University GottingenGottingenGermany Department of Rheum atology and Immunology Hannover Medical SchoolHannoverGermany Public Health Department HannoverGermany Department of Pneumology and German Centre of Lung Research(DZL) Hannover Medical SchoolHannoverGermany German Center for Infection Research(DZIF) partner site Hannover-BraunschweigHannoverGermany cluster of excellence resist(EXC 2155) Hannover Medical SchoolHannoverGermany

Neutralizing antibodies targeting the receptor-binding domain(RBD)of the SARS-CoV-2 spike(S)block severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into cells via surface-expressed angiotensin-converting enzyme 2(ACE2).We used a surrogate virus neutralization test(sVNT)and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus(VSV)vector-based neutralization assay(pVNT)to assess the degree to which serum antibodies from coronavirus disease 2019(COVID-19)convalescent patients interfere with the binding of SARS-CoV-2 S to *** tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent ***,sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA ***,levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient *** to pVNT,sVNT is less sophisticated and does not require any biosafety *** this assay is also much faster and cheaper,sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

关键词： COVID-19 SARS-CoV-2 Neutralizing antibody Serum ELISA

Promotion of Arabidopsis immune responses by a rhizosphere fungus via supply of pipecolic acid to plants and selective augment of phytoalexins

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Science China(Life Sciences) 2023年第5期66卷 1119-1133页

作者： Feifei Luo Guirong Tang Song Hong Tianyu Gong Xiu-Fang Xin Chengshu Wang Key Laboratory of Insect Developmental and Evolutionary Biology CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China CAS Center for excellence in Biotic Interactions University of Chinese Academy of SciencesBeijing 100049China National key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

The ascomycete insect pathogenic fungi such as Metarhizium species have been demonstrated with the abilities to form the rhizosphere or endophytic relationships with different plants for nutrient *** this study,after the evident infeasibility of bacterial disease development in the boxed sterile soils,we established a hydroponic system for the gnotobiotic growth of Arabidopsis thaliana with the wild-type and transgenic strain of Metarhizium *** transgenic fungus could produce a high amount of pipecolic acid(PIP),a pivotal plant-immune-stimulating *** inoculation experiments showed that *** could form a non-selective rhizosphere relationship with *** to the PIP uptake by plants after exogenous application,PIP level increased in Col-0 and could be detected in the PIP-non-producing Arabidopsis mutant(ald1)after fungal inoculations,indicating that plants can absorb the PIP produced by *** transgenic fungal strain had a better efficacy than the wild type to defend plants against the bacterial pathogen and aphid *** to ald1,fmo1 plants could not be boosted to resist bacterial infection after *** fungal inoculations,the phytoalexins camalexin and aliphatic glucosinolate were selectively increased in Arabidopsis via both PIP-dependent and-independent *** study unveils the potential mechanism of the fungus-mediated beneficial promotion of plant immunity against biological *** data also highlight the added values of *** to plants beyond the direct suppression of insect pest populations.

关键词： Metarhizium robertsi rhizosphere fungus pipecolic acid camalexin aliphatic glucosinolate plant defenses