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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

Hide and seek with SARS-CoV-2: spike receptor-binding domain-specific memory B cells still recognize Omicron variant

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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

Dual role for atypical chemokine receptor 1 in myeloid cell hematopoiesis and distribution

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Cellular & Molecular Immunology 2018年第4期15卷 399-401页

作者： Marc Permanyer Berislav Bošnjak reinhold förster Institute of Immunology Hannover Medical SchoolCarl-Neuberg-Strabe 1Hannover 30625Germany

Similar to conventional chemokine receptors,atypical chemokine receptors(ACKRs)are cell-surface receptors that possess a seven transmembrane domain structure and regulate immune responses by interacting with ***,ACKRs differ from conventional chemokine receptors because of their inability to couple to G proteins and therefore to transduce intracellular signals mediating leukocyte migration upon chemokine ***,ACKRs internalize,transport or scavenge chemokines,regulating their extracellular availability,and thus impacting homeostasis,inflammation and immune response.

关键词： chemokine atypical homeostasis

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

Application of light sheet microscopy for qualitative and quantitative analysis of bronchus-associated lymphoid tissue in mice

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Cellular & Molecular Immunology 2018年第10期15卷 875-887页

作者： David Twapokera Mzinza Henrike fleige Kristin Laarmann Stefanie Willenzon Jasmin Ristenpart Julia Spanier Gerd Sutter Ulrich Kalinke Peter Valentin-Weigand reinhold förster Institute of Immunology Hannover Medical SchoolHannoverGermany Institute for Microbiology University of Veterinary Medicine HannoverHannoverGermany Institute for Experimental Infection Research TWINCORECentre for Experimental and Clinical Infection Researcha joint venture between the Helmholtz-Centre for Infection Research and the Hannover Medical SchoolHannoverGermany Institute for Infectious Diseases and Zoonoses University of Munich LMUMunichGermany

Bronchus-associated lymphoid tissue(BALT)develops at unpredictable locations around lung bronchi following pulmonary *** formation and composition of BALT have primarily been investigated by immunohistology that,due to the size of the invested organ,is usually restricted to a limited number of histological *** assess the entire BALT of the lung,other approaches are urgently ***,we introduce a novel light sheet microscopy-based approach for assessing lymphoid tissue in the *** antibody staining of whole lung lobes and optical clearing by organic solvents,we present a method that allows in-depth visualization of the entire bronchial tree,the lymphatic vasculature and the immune cell composition of the induced ***,three-dimensional analysis of the entire lung allows the qualitative and quantitative enumeration of the induced *** this approach,we show that a single intranasal application of the replication-deficient poxvirus MVA induces BALT that constitutes up to 8%of the entire lung volume in mice deficient in CCR7,in contrast to wild type mice(WT).furthermore,BALT induced by heat-inactivated *** is dominated by a pronounced T cell infiltration in Cxcr5-deficient mice,in contrast to WT mice.

关键词： Lung BALT light sheet microscopy E.coli MVA

APPROXIMATING THE STATIONARY BELLMAN EQUATION BY HIERARCHICAL TENSOR PRODUCTS

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Journal of Computational Mathematics 2024年第3期42卷 638-661页

作者： Mathias Oster Leon Sallandt reinhold Schneider Technische Universität Berlin Strasse des 17.Juni 13510623 BerlinGermany

We treat infinite horizon optimal control problems by solving the associated stationary Bellman equation numerically to compute the value function and an optimal feedback *** dynamical systems under consideration are spatial discretizations of non linear parabolic partial differential equations(PDE),which means that the Bellman equation suffers from the curse of *** non linearity is handled by the Policy Iteration algorithm,where the problem is reduced to a sequence of linear equations,which remain the computational bottleneck due to their high *** reformulate the linearized Bellman equations via the Koopman operator into an operator equation,that is solved using a minimal residual *** the Koopman operator we identify a preconditioner for operator equation,which deems essential in our numerical *** overcome computational infeasability we use low rank hierarchical tensor product approximation/tree-based tensor formats,in particular tensor trains(TT tensors)and multi-polynomials,together with high-dimensional quadrature,*** controlling a destabilized version of viscous Burgers and a diffusion equation with unstable reaction term numerical evidence is given.

关键词： feedback control Dynamic programming Hamilton-Jacobi-Bellman Tensor product approximation Variational Monte-Carlo

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

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

Changes in children’s cardiorespiratory fitness and body mass index over the course of the COVID‑19 pandemic:a 34‑month longitudinal study of 331 primary school children

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World Journal of Pediatrics 2024年第2期20卷 185-188页

作者： Gerald Jarnig reinhold Kerbl Mireille N.M.van Poppel Institute of Human Movement Science Sport and HealthUniversity of GrazMozartgasse 148010 GrazAustria Department of Pediatrics and Adolescent Medicine LKH Hochsteiermark8700 LeobenAustria

In late 2019,heavy restrictions were enforced on public activities worldwide to diminish the spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus[1].These restrictions,which included school closures and strictly limited sports and leisure opportunities,particularly impacted children and adolescents[2].Lifestyle changes in children and adolescents led to reduced physical activity levels[2,3],increased sedentary behavior[3,4],changes in eating habits,and changes in sleep habits[3].

关键词： respiratory acute children

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