HIV-infected H9 T cell

Future Topic: Immunology & Inflammation

The Initiative and Networking Fund of the Helmholtz Association

The Initiative

Five Helmholtz Centers are joining forces in a new initiative that aims to advance immunology research and the development of new therapies. The MDC is coordinating the long-term project, which was launched in November 2017 with a three-year program.

There is a mood of optimism among the immunology community, because the past few years have seen great strides made in immune system research. The first immunology therapies have been approved, while others are being tested in clinical trials. Researchers are uncovering ever more details about the complex system of organs, tissues, and different cell types that make up the human immune system.

The initiative entitled “Immunology & Inflammation” brings together immunology research – which is spread out over various Helmholtz Centers – in a common structure. Of twenty projects, six are organized as “tandem” projects in which laboratories of different Centers work closely together.

MDC researchers Michela Di Virgilio and Klaus Rajewsky are leading and coordinating the initiative. It is the nucleus for an undertaking that intends to position the Helmholtz Association as a main player in application-oriented immunology research internationally.

 

Key scientific questions addressed by the initiative

  • How is the tissue specificity of immune cells generated and how is it affected by environmental influences, plasticity and the tissue microenvironment? 

  • What is the mechanistic link between infections, immune reactions and their microenvironment, inflammatory responses and central nervous system disorders, including neurodegenerative disease, and how can we use this information to better understand and treat these disorders? 

  • How can our knowledge of the immune system be applied to develop innovative therapies, including the identification of novel antigens for immune therapies and gene repair strategies in monogenic immune diseases?

The Helmholtz Centres have a broad repertoire of state-of-the-art technologies and expertise to work on these topics. Examples are CRISPR/Cas9-mediated mutagenesis, genetic mouse models, cell-fate-mapping, organoids and tumor explants, as well as GMP production of pharmaceuticals and many years of experience in conducting clinical studies.

Aside from new and joint research projects, the training of the next generation of basic and clinical researchers in immunology, as well as scientific exchange, is also in the focus of the future topic.

Featured picture: Scanning electromicrograph of an HIV-infected H9 T cell. Credit: NIAID, cc-by-2.0

Team

These 23 research teams are taking part in the initiative:

Max Delbrück Center for Molecular Medicine (MDC)

The MDC is devoted to understanding the molecular basis of health and disease, with a focus on disease mechanisms at a system-wide level and the translation of findings into clinical applications.

It cooperates closely with Charité, a large university hospital in Berlin. Joint institutions include the Experimental and Clinical Research Center (ECRC ) und the Berlin Institute of Health (BIH).

One of the research areas at the MDC is immunology and inflammation, which covers tumor immunology, DNA repair in B lymphocytes, the role of tumor stroma-immune cell interaction in cancers, the role of innate immune cells in gliomas and neurodegenerative diseases, and the development of immunotherapy strategies.

The MDC’s participating research groups bring a broad range of technological expertise to the initiative – ranging from biochemical assays, structure and function analysis, and gene editing to the development of preclinical mouse models, GMP production, and even clinical trials.

German Cancer Research Center (DKFZ)

The DKFZ is a multidisciplinary center covering cancer biology from basic molecular and cell biology to clinical research and care.

Through the National Center for Tumor Diseases, a joint venture between the DKFZ, Heidelberg University Hospital, and German Cancer Fund, the DKFZ has access to patients for research from bench to bedside and back. The participating groups of the DKFZ bring in broad expertise in fundamental and clinical tumor immunology, the link between cancer, chronic inflammation and viral infection, neuroimmunology, and immune surveillance of tumors.

The center will contribute technological expertise crucial to the success of the proposal, such as the generation and characterization of pre-clinical mouse models, in vivo fate mapping, GMP production, and innovative clinical trials.

German Center for Neurodegenerative Diseases (DZNE)

The DZNE focuses on neurodegenerative disease, covering both research on the fundamental molecular and cellular basis of neurodegenerative disease as well as clinical and population research.

The participating groups cover an especially exciting area of research, namely the link between innate immune and inflammatory mechanisms to neurodegenerative disease. The center will provide expertise on profiling neurodegeneration, neuroinflammation and neuronal function including in vivo imaging, CNS histology, generation of human-derived cellular models, and their functional assessment under physiological and pathological circumstances.

Helmholtz Zentrum München (HMGU)

The HMGU aims to contribute significantly to a better understanding of major non-communicable common diseases which develop from lifestyle, environmental factors and personal genetic background, most notably diabetes and allergy.

The overall goal of HMGU’s research is to elucidate the complex disease causes and to develop innovative approaches for their precise diagnosis, prevention and therapy. The participating groups bring in their expertise in the basic molecular mechanisms of T cell signaling, activation, and tolerance, as well as T cell immunity and immunotherapy in diabetes, allergy and lung diseases.

The center will contribute important technological expertise in the generation and provision of novel pre-clinical mouse models, tools to fate map tumor cells and immune cells, and a translational approach for CRISPR/Cas9-based gene therapy of monogenic diseases.

Helmholtz Centre for Infection Research (HZI)

The HZI has expertise in the area of infectious diseases, investigating the fundamental principles underlying infection processes to develop innovative approaches to prevent, diagnose and treat infectious diseases.

In this context, the host’s innate and adaptive immune responses to infection, evasion mechanisms that allow pathogens to circumvent the host defenses, and underlying mechanisms of pathogen clearance are dissected.

Within this proposal, the HZI will contribute expertise in epigenetic imprinting for the identification of immune cell subsets, epigenome-editing of T cells using CRISPR/Cas9, predictive mathematical models, mouse behavioral analysis, as well as expertise in clinical trials and GMP production of antibodies and immune cells.

Research

Inflammation processes and interactions between the adaptive and innate immune systems play a major role in both infections and cancers – as well as in nearly every widespread human disease.

Since a comprehensive approach to the immune system would be as complex as the system itself, we concentrate on three interconnected central and timely topics in immunology, which are addressed in three scientific work packages (WP).

WP 1. Tissue-Specific Immune Cells

WP1 concerns the factors that determine the tissue- and organ-specificity of immune cells, a topic that is gaining rapidly increasing attention and may become ever more central in understanding as well as treating immune-related diseases. Decisive factors will be tackled in the following aims:

  1. the genetically determined developmental programs that lead to immune cell specificity and function,
  2. the influence of external (environmental) factors on innate and adaptive immunity and its plasticity,
  3. the effects and mediators of the tissue microenvironment in shaping immune cell functions, and
  4. as a specific example the interplay of tumor microenvironment and cancer cells, which allows the latter to escape immune surveillance.

WP 2. Immunity, Infection and Inflammation in the CNS

WP2 explores a second major example of the impact of a specific environment on the immune system by addressing the characteristics of immunity, infection and inflammation in the central nervous system (CNS), processes that have recently been demonstrated to play major roles in many CNS disorders, notably neurodegeneration, but also neuropsychiatric diseases. Its specific aims concern

  1. functional and regional diversity of microglia, the innate immune cells of the CNS,
  2. microglia-mediated inflammation as a major causative mechanism in neurodegenerative disorders, and
  3. the interplay between infection and neurodegeneration, an interplay that occurs both in CNS-based and peripheral infection.

WP 3. Innovative Therapies

WP3 addresses innovative therapies that result from research of WP1 and WP2 and enables the translation of these findings into the clinic. Based on the first, currently ongoing clinical trials of such innovative therapeutic strategies, notably in cancer, the specific aims of WP3 will cover

  1. harnessing the adaptive and innate immune response against tumors,
  2. the search for and characterization of novel antigens for targeted T cell therapy, the bottleneck in cellular therapies, and
  3. CRISPR-Cas9 mediated gene therapy of monogenic immunodeficiencies as pioneer projects.

Synergies

A key aim of the initiative is to bring together a community of excellent researchers from all centers in the Helmholtz Research Field Health.

Several collaborative efforts within the consortium already exist and have yielded results which could not have been achieved by single research groups. Examples include common studies investigating connections between infections (HZI) and neurodegeneration (DZNE), or studies on the role of inflammation in metastasis and dissemination of tumor cells (DKFZ) and (MDC), as well as the role of chronic inflammation (DKFZ) and programed cell death in controlling DNA damage (MDC).

To enable and foster projects that cannot be done at a single Helmholtz Center, we have enhanced interactions by funding six collaborative projects, i.e. projects implemented by pre- and/or post-doctoral researchers who are supervised by two PIs from different centers:

  • TCR gene therapy of pancreatic cancer through coordinated attack by mutanome-specific CD8+ and p53-specific CD4+ T-cell. Supervisors: Rienk Offringa (DKFZ) and Thomas Blankenstein (MDC)

  • A combined in vitro and in silico analysis of microglia activation to assess the potential of the voltage-gated proton channel HVCN1 as a therapeutic target in Alzheimer’s disease. Supervisors: Melania Capasso (DZNE) and Michael Meyer-Hermann (HZI)

  • Impact of AHR signalling on immunity. From structure to function. Supervisors: Michael Platten (DKFZ) and Oliver Daumke (MDC)

  • Mechanistic analysis of lymphoma-triggered dissemination to brain, liver and lymphoid tissue through crosstalk to stromal cells. Supervisors: Mathias Heikenwälder (DKFZ) and Uta Höpken (MDC)

  • Impact of nasal pollen exposure on the inflammatory milieu within the brain and the control of neurotropic virus infections (NaPo-BRAIN). Supervisors: Claudia Traidl-Hoffmann (HMGU) and Ulrich Kalinke(HZI)

  • Towards therapeutic gene editing in monogenic primary immunodeficiencies. Supervisors: Klaus Rajewsky (MDC) and Ellen Renner (HMGU)

Activities

I & I Symposium on Covid-19

March 3, 2021, virtual

I & I  3rd Retreat

September 30 - 1. October 2020

The 2020 I&I retreat will be held online. Please, follow the link below to register yourself.

I & I Talks and Lab Visits

 

PhD students and postdocs from the participating labs are invited to go to a partner lab to give a talk and visit the lab.

 

Training Schools

 

PhD students and early-stage postdocs from the participating labs are invited to attend a training school. The project will also cover the attendance to Conferences and Workshops as long as the participant presents a poster or gives a talk. 

Recommended schools:

  • FEBS Immunology Summer School Link 
  • Schools organized by the DGfI Link 
  • Schools organized by the European Network of Immunology Institutes Link 

I & I 2nd Retreat

October 2019, Heidelberg

The info will be available soon.

Satellite Symposium - DGfI Meeting

September 10, 2019, Munich

All I & I researchers are welcome to join the Immunology & Inflammation Satellite Symposium that takes place in Munich on September 10, 2019. The Symposium is organized by Prof. Ellen Renner and Prof. Klaus Rajewsky. 

See the Program here. 

You can access the conference website here. 

1st I & I Conference

February 24-26, 2019, Berlin

Our 1st edition holds an exciting program that comprises four sessions covering the key new developments, their impact on life science, and implications for modern medicine. We have invited scientists among the top world-renowned experts for their standing in the field and contribution to the breakthroughs that fuelled these new areas of investigation. Young scientists will also be given the opportunity to present data through posters and short presentations. 

You can access the conference website here.

I & I 1st Retreat

November 26-27, 2017, Berlin

The I&I kick-off meeting and 1st retreat took place on 26-27 November 2017 at the Conference Venue of the Max Planck Society, Berlin. The consortium principal investigators were invited to shortly share their research work.

The agenda is available here.

Publications

July 2021, bioRxiv
Loss of TREM2 reduces hyperactivation of progranulin deficient microglia but not lysosomal pathology
A. Reifschneider, S. Robinson, B. van Lengerich, J. Gnörich, [...] C. Haass

 

July 2021, Allergy
Immunological effects of adjuvanted low-dose allergoid allergen-specific immunotherapy in experimental murine house dust mite allergy
A. Heldner, F. Alessandrini, D. Russkamp, S. Heine, B. Schnautz, [...] C. B. Schmidt-Weber, S. Blank

 

July 2021, Cell Mol Gastroenterol Hepatol
Pancreatic cancer chemotherapy is potentiated by induction of tertiary lymphoid structures in mice
F. R. Delvecchio, R. E. A. Fincham, S. Spear, A. Clear, M. Roy-Luzarraga, [...] M. Capasso, H. M. Kocher

 

July 2021, bioRxiv
Clostridium difficile Toxin B activates the NLRP3 inflammasome in human macrophages, demonstrating a novel regulatory mechanism for the Pyrin inflammasome
M. S.J. Mangan, F. Gorki, K. Krause, A. Alexander, T. Ebert, D. Jahn, [...] E. Latz

 

July 2021, Brain Pathol
Transcriptome analysis following neurotropic virus infection reveals faulty innate immunity and delayed antigen presentation in mice susceptible to virus-induced demyelination. In revision. Brain Pathology
M. Ciurkiewicza, S. Floess, M. Beckstette, M. Kummerfeld, W. Baumgärtner, J. Huehn*, A. Beineke*

 

June 2021, Communications Medicine
High SARS-CoV-2 seroprevalence in children and adults in the Austrian ski resort of Ischgl
L. Knabl, T. Mitra, J. Kimpel, A. Rössler, A. Volland, H. Walser, […] M. Meyer-Hermann, D. von Laer

 

June 2021, Sci Immunol
MyD88 signaling by neurons induces chemokines that recruit protective leukocytes to the virus-infected CNS
L. Ghita, J. Spanier, C. Chhatbar, F. Mulenge, A. Pavlou, P. K. Larsen, […] U. Kalinke

 

June 2021, Cell Rep
Il-37 Reduces Neuroinflammation and Rescues Cognitive Impairment in an Alzheimer's Disease Model
N. Lonnemann, S. Hosseini, M. Ohm, K. Hiller, C. Dinarello, M. Korte

 

June 2021, Glia
Histamine triggers microglial responses indirectly via astrocytes and purinergic signaling
P. Xia, F. Logiacco, Y. Huang, H. Kettenmann, M. Semtner

 

June 2021, J Allergy Clin Immunol
Distinct cytokine profiles associated with COVID-19 severity and mortality
K. Dorgham*, M. Gökkaya*, P. Quentric*, […] C. Traidl-Hoffmann, G. Gorochov*, A. U. Neumann*

 

June 2021, Nature Med
XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis
A. Deczkowska, E. David, P. Ramadori, D. Pfister, M. Safran, [...] M. Heikenwälder, E. Elinav, I. Amit

 

May 2021, Nature Cancer
Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas
M. Friedrich, R. Sankowski, L. Bunse, M. Kilian, […] M. Prinz, M. Platten

 

May 2021, Hepatology
HIF1α‐mediated RelB/APOBEC3B downregulation allows Hepatitis B Virus persistence
T. Riedl, S. Faure-Dupuy, M. Rolland, S. Schuehle, Z. Hizir, S. Calderazzo, X. Zhuang, [...] M. Heikenwälder

 

May 2021, Med
The therapeutic landscape of hepatocellular carcinoma
S. Gallage, M. García-Beccaria, M. Szydlowska, M. Rahbari, R. Mohr, F. Tacke, M. Heikenwälder

 

April 2021, Front Cell Neurosci
Long-Term Consequence of Non-neurotropic H3N2 Influenza A Virus Infection for the Progression of Alzheimer’s Disease Symptoms
S. Hosseini, K. Michaelsen-Preusse, K. Schughart, M. Korte

 

April 2021, Neuron
Loss of TREM2 facilitates tau accumulation, spreading, and brain atrophy, but only in the presence of amyloid pathology
C. Haass

 

April 2021, Front Immunol
Editorial: Novel Advances in Allergy Diagnosis and Treatment
S. Blank, C. Hilger

 

April 2021, Cell Stem Cell
Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly
V. Krenn, C. Bosone, T. Burkard, J. Spanier, U. Kalinke, A. Calistri, C. Salata, R. Christoff, P. Garcez, A. Mirazimi, J. Knoblich

 

April 2021, CRISPR J
Rescue of STAT3 Function in Hyper-IgE Syndrome Using Adenine Base Editing
A. C. Eberherr, A. Maaske, C. Wolf, F. Giesert, R. Berutti, E. Rusha,  [...] E. D. Renner

 

April 2021, Nature
A vaccine targeting mutant IDH1 in newly diagnosed glioma
M. Platten, L. Bunse, A. Wick, T. Bunse, L. Le Cornet, [...] W. Wick

 

April 2021, Nature
NASH limits anti-tumour surveillance in immunotherapy-treated HCC
D. Pfister, N. G. Núñez, R. Pinyol, O. Govaere, M. Pinter, M. Szydlowska, R. Gupta, [...] M. Heikenwälder

 

March 2021, PNAS
Higher airborne pollen concentrations correlated with increased SARS-CoV-2 infection rates, as evidenced from 31 countries across the globe
A. Damialis, S. Gilles, M. Sofiev, V. Sofieva, F. Kolek, […] COVID-19/Pollen study group, C. Traidl-Hoffmann

 

February 2021, Allergy
Allergen-specific immunotherapy induces the suppressive secretoglobin 1A1 in cells of the lower airways
U. M. Zissler, C. A. Jakwerth, F. Guerth, L. Lewitan, [...] C. B. Schmidt-Weber, A. M. Chaker

 

January 2021, BMC Med
Development of the reproduction number from coronavirus SARS-CoV-2 case data in Germany and implications for political measures
S. Khailaie*, T. Mitra*, A. Bandyopadhyay, […] S. C. Binder*, M. Meyer-Hermann*

 

January 2021, Cell Rep
Astrocytes and oligodendrocytes in the thalamus jointly maintain synaptic activity by supplying metabolites.
C. Philippot, S. Griemsmann, R. Jabs, G. Seifert, H. Kettenmann, C. Steinhäuser

 

January 2021, Nature Communications
CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells
M. Bunse, J. Pfeilschifter, J. Bluhm, M. Zschummel, […] A. Rehm, U. E. Höpken

 

January 2021, J Neurosci Res
Glial cell line-derived neurotrophic factor increases matrix metallopeptidase 9 and 14 expression in microglia and promotes microglia-mediated glioma progression
Y. Huang, B. Zhang, H. Haneke, […] O. Dzaye, F. Hu, H. Kettenmann

 

January 2021, J Clin Invest
mTOR-dependent translation amplifies microglia priming in aging mice
L. Keane, I. Antignano, S.-P. Riechers, [...] M. T. Heneka, M. Capasso

 

December 2020, PNAS
The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer's disease
N. Lonnemann, S. Hosseini, C. Marchetti, D. B. Skouras, D. Stefanoni, A. D'Alessandro, C. A. Dinarello, M. Korte

 

December 2020, Cell Host Microbe
Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies
M. Cortese, J. Y. Lee, B. Cerikan, C. J. Neufeldt, V. M. J. Oorschot, S. Köhrer, [...] R. Bartenschlager

 

December 2020, Clinical Immunology
Class switch recombination defects: impact on B cell maturation and antibody responses
E. D. Renner, C. E. Krätz, J. S. Orange, [...] T. R. Torgerson, H. D. Ochs

 

December 2020, Front Immunol
B-Cell-Specific Myd88 L252P Expression Causes a Premalignant Gammopathy Resembling IgM MGUS
K. Schmidt, U. Sack, R. Graf, W. Winkler, O. Popp, […] Klaus Rajewsky

 

December 2020, J Nucl Med
Asymmetry of fibrillar plaque burden in amyloid mouse models
C. Sacher, T. Blume, L. Beyer, G. Biechele, J. Sauerbeck, F. Eckenweber, M. Deussing,  […] C. Haass, P. Bartenstein, P. Cumming, A. Rominger, J. Herms, M. Brendel

 

2020, Exp Cell Res
Down-regulation of Aquaporin-1 mediates a microglial phenotype switch affecting glioma growth.
F. Hu, Y. Huang, M. Semtner, K. Zhao, Z. Tan, O. Dzaye, H. Kettenmann, K. Shu, T. Lei

 

November 2020, Immunohorizons
Amelioration of Murine Autoimmune Pancreatitis by Targeted LTβR Inhibition and Anti-CD20 Treatment
G. M. Wanner-Seleznik, T. Reding, R. Chen, A. K. Gupta, D. Lenggenhager, J. Browning, S. Segerer, M. Heikenwälder, R. Graf

 

December 2020, Nature
Inhibition of LTβR signalling activates WNT-induced regeneration in lung
T. M. Conlon, G. John-Schuster, D. Heide, D. Pfister, […] M. Heikenwälder, A. Ö. Yildirim

 

October 2020, Neuron
Emerging Microglia Biology Defines Novel Therapeutic Approaches for Alzheimer’s Disease
J. W. Lewcock, K. Schlepckow, G. Di Paolo, S. Tahirovic, K. M. Monroe, C. Haass

 

October 2020, iScience
An Adaptive Control Scheme for Interleukin-2 Therapy
S. Khailaie, G. Montaseri, M. Meyer-Hermann
 

October 2020, Molecular Neurodegeneration
Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration
N. Franzmeier, M. Suárez-Calvet, L. Frontzkowski, A. Moore, T. J. Hohman, E. Morenas-Rodriguez,  […] C. Haass, M. Ewers

 

October 2020, Neurobiol Dis
Neurofibromatosis 1 - Mutant microglia exhibit sexually-dimorphic cyclic AMP-dependent purinergic defects.
N. Elmadany, F. Logiacco, A. Buonfiglioli, V. Haage, E.C. Wright-Jin, A. Schattenberg, R. Papawassiliou, H. Kettenmann, M. Semtner, D.H. Gutmann

 

September 2020, EMBO Reports
Loss of TMEM106B potentiates lysosomal and FTLD‐like pathology in progranulin‐deficient mice
G. Werner, M. Damme, M. Schludi, [...] C. Haass, A. Capell
 

September 2020, Brain Behavior and Immunity
Deletion of muscarinic acetylcholine receptor 3 in microglia impacts brain ischemic injury
A. Costa, V. Haage, S. Yang, [...] S. A. Wolf, H. Kettenmann

 

September 2020, Orphanet J Rare Dis
Retained primary teeth in STAT3 hyper-IgE syndrome: early intervention in childhood is essential
I. Meixner, B. Hagl, C. I. Kröner, B. D. Spielberger, E. Paschos, G. Dückers, T. Niehues, R. Hesse, E. D. Renner

 

September 2020, Acta Neuropathologica Communications
Activation of Toll-like receptor 5 in microglia modulates their function and triggers neuronal injury
M. Ifuku, L. Hinkelmann, L. D. Kuhrt, [...] H. Kettenmann, L. S. Helmut
 

September 2020, Allergy
Pollen induces reactivation of latent herpesvirus and differentially affects infected and uninfected murine macrophages
J.D. Speidel, S. Gilles, B.  Steer, […] C. Traidl-Hoffmann, H. Adler

 

September 2020, Cell Stem Cell
Resolving Fates and Single-Cell Transcriptomes of Hematopoietic Stem Cell Clones by PolyloxExpress Barcoding
W. Pei, F. Shang, X. Wang, A. K. […] H. R. Rodewald

 

September 2020, J Allergy Clin Immunol
Defining biomarkers to predict symptoms in subjects with and without allergy under natural pollen exposure
M. Gökkaya, A. Damialis, T. Nussbaumer, [...] A. U. Neumann, C. Traidl-Hoffmann, S. Gilles

 

August 2020, Front Immunol
Predicting Success of Allergen-Specific Immunotherapy
U. M. Zissler, C. B. Schmidt-Weber

 

August 2020, Biophys J
Mathematical model shows how sleep may affect amyloid β fibrillization
M. Hoore, S. Khailaie, G. Montaseri, T. Mitra, M. Meyer-Hermann

 

August 2020, medRxiv
The Common Interests of Health Protection and the Economy: Evidence from Scenario Calculations of COVID-19 Containment Policies
F. Dorn, S. Khailaie, M. Stoeckli, S. Binder, B. Lange, […] M. Meyer-Hermann

 

August 2020, J Neurosci
Synergistic Toll-like Receptor 3/9 Signaling Affects Properties and Impairs Glioma-Promoting Activity of Microglia
Y. Huang, Q. Zhang, M. Lubas, Y. Yuan, F. Yalcin, I. E. Efe, […] F. Hu, H. Kettenmann

 

August 2020, Molecular Therapy
CRISPR-Cas9-Mediated ELANE Mutation Correction in Hematopoietic Stem and Progenitor Cells to Treat Severe Congenital Neutropenia
N. T. Tran, R. Graf, A. Wulf-Goldenberg, [...] K. Rajewsky, V. T. Chu

 

August 2020, Sci Rep
Signaling via the p75 neurotrophin receptor facilitates amyloid-beta-induced dendritic spine pathology
A. Patnaik, M. Zagrebelsky, M. Korte, A. Holz

 

July 2020, Transl Psychiatry
Neuroinflammatory alterations in trait anxiety: modulatory effects of minocycline.
S. Rooney, A. Sah, M.S. Unger, M. Kharitonova, S.B. Sartori, C. Schwarzer, L. Aigner, H. Kettenmann, S.A. Wolf, N. Singewald

 

July 2020, bioRxiv
SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-kB
C. J. Neufeldt, B. Cerikan, M. Cortese, J. Frankish, J.-Y. Lee, […] N. Halama, U. Merle, M. Boutros, M. Binder, R. Bartenschlager

 

July 2020, PLoS Pathog
Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV
S. J. Theobald, C. Kreer, S. Khailaie, A. Bonifacius, […] M. Meyer-Hermann, F. Klein, R. Stripecke

 

July 2020, Current Allergy and Asthma Reports
Antigen 5 Allergens of Hymenoptera Venoms and Their Role in Diagnosis and Therapy of Venom Allergy
S. Blank, M. L. Bazon, J. Grosch, C. B. Schmidt-Weber, M. R. Brochetto-Braga, M. B. Bilò, T. Jakob

 

July 2020, J Neurosci
Enduring Changes in Neuronal Function upon Systemic Inflammation Are NLRP3 Inflammasome Dependent
M. M. S. Beyer, N. Lonnemann, A. Remus, E. Latz, M. T. Heneka, M. Korte

 

July 2020, Gastroenterology
MCL1 Is Required for Maintenance of Intestinal Homeostasis and Prevention of Carcinogenesis in Mice
M. E. Healy, Y. Boege, M C. Hodder, F. Böhm, M. Malehmir, A. L. Scherr, [...] M. Heikenwälder*, A. Weber*

 

July 2020, Journal of Experimental Medicine
PDGFA-associated protein 1 protects mature B lymphocytes from stress-induced cell death and promotes antibody gene diversification
V. Delgado-Benito, M. Berruezo-Llacuna, R. Altwasser, [...] A. Akalin, M. Di Virgilio

 

June 2020, STAR Protocols
Protocol for Efficient CRISPR/Cas9/AAV-Mediated Homologous Recombination in Mouse Hematopoietic Stem and Progenitor Cells
N. T. Tran, J. Trombke, K. Rajewsky, V. T. Chu
 

June 2020, Current Allergy and Asthma Reports
The honeybee venom major allergen Api m 10 (icarapin) and its role in diagnostics and treatment of Hymenoptera venom allergy
T. Jakob, M. M. Rauber, A. Perez-Riverol, E. Spillner, S. Blank

 

June 2020, PNAS
Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis
T. Sommermann, T. Yasuda, J. Ronen, T. Wirtz, [...] A. Akalin, K. Rajewsky

 

May 2020, The Journal of Pathology
Deficiency in IκBα in the intestinal epithelium leads to spontaneous inflammation and mediates apoptosis in the gut
N. Mikuda, R. Schmidt‐Ullrich, [...] J. Wolf, U. E. Höpken, C. Scheidereit, A. A. Kühl, M. Kolesnichenko

 

May 2020, Toxins
Shedding Light on the Venom Proteomes of the Allergy-Relevant Hymenoptera Polistes dominula (European Paper Wasp) and Vespula spp. (Yellow Jacket)
J. Grosch, C. Hilger, M. B. Bilò, [...] C. B. Schmidt-Weber, S. Blank
 

May 2020, Nat Commun
Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy
D. Baumann, T. Hagele, J. Mochayedi, J. Drebant, […] O. Strobel, R. Offringa

 

May 2020, Cell Reports
Type I Interferon Receptor Signaling in Astrocytes Regulates Hippocampal Synaptic Plasticity and Cognitive Function of the Healthy CNS
S. Hosseini, K. Michaelsen-Preusse, [...] U. Kalinke, M. Korte

 

May 2020, J Heptaol
A dual role for hepatocyte-intrinsic canonical NF-κB signaling in virus control
S. Namineni, T. O'Connor, S. Faure-Dupuy, P. Johansen, [...] U. Kalinke, P. A. Knolle, M. Heikenwälder

 

May 2020, Cell Reports
hGBP1 Coordinates Chlamydia Restriction and Inflammasome Activation through Sequential GTP Hydrolysis
A. Xavier, M.A. Al-Zeer, T.F. Meyer, O. Daumke

 

April 2020, J Neurosci
The VGF-derived Peptide TLQP21 Impairs Purinergic Control of Chemotaxis and Phagocytosis in Mouse Microglia
N. Elmadany, F. de Almeida Sassi, S. Wendt, F. Logiacco, […] H. Kettenmann, M. Semtner

 

April 2020, Int J Mol Sci
O-Vanillin Attenuates the TLR2 Mediated Tumor-Promoting Phenotype of Microglia.
P. Triller, J. Bachorz, M. Synowitz, H. Kettenmann, D. Markovic

 

April 2020, Scientific Reports
Vitamin C supports conversion of human γδ T cells into FOXP3-expressing regulatory cells by epigenetic regulation
L. Kouakanou, C. Peters, [...] J. Huehn, D. Kabelitz

 

March 2020, World Allergy Organization Journal
Physical and immunological barrier of human primary nasal epithelial cells from non-allergic and allergic donors
C. Bergougnan, D. C. Dittlein, [...] C. Traidl-Hoffmann, S. Gilles

 

March 2020, Allergy
Pollen exposure weakens innate defense against respiratory viruses
S. Gilles, C. Blume, M. Wimmer, A. Damialis, L. Meulenbroek, M. Gökkaya, […] C. Traidl-Hoffmann

 

February 2020, Immunity
Human Mast Cell Proteome Reveals Unique Lineage, Putative Functions, and Structural Basis for Cell Ablation
T. Plum, X. Wang, M. Rettel, J. Krijgsveld, T. B. Feyerabend, H.-R. Rodewald

 

February 2020, Allergy
Nasal-specific IgE correlates to serum-specific IgE: First steps toward nasal molecular allergy diagnostic
M. Gökkaya, V. Schwierzeck , K. Thölken, [...] C. Traidl‐Hoffmann, S. Gilles

 

February 2020, Cell Death Dis
Hepatocyte apoptosis is tumor promoting in murine nonalcoholic steatohepatitis
P. Hirsova, F. Bohm, E. Dohnalkova, B. Nozickova, M. Heikenwälder, G. Gores, A. Weber

 

February 2020, Nature Communications
Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas
K. Aslan, V. Turco, […] M. Platten

 

February 2020, PLoS Pathogens
Selective reconstitution of IFNγ gene function in Ncr1+ NK cells is sufficient to control systemic vaccinia virus infection
K. Borst, S. Flindt, P. Blank, [...] U. Kalinke

 

February 2020, J Neurosci Res
Microglial phagocytosis in aging and Alzheimer's disease
E. Gabande Rodriguez, L. Keane, M. Capasso

 

January 2020, Allergy
Impact of high-altitude therapy on type-2 immune responses in asthma patients
T. Boonpiyathad, G. Capova, H. W. Duchna, A. L. Croxford, H. Farine, [...] E. D. Renner, C. A. Akdis

 

January 2020, bioRxiv
Murine Staphylococcus aureus chronic infection is cured by theory-driven therapy
L. A. Papaxenopoulou, G. Zhao, S. Khailaie, […] M. Meyer-Hermann

 

January 2020, bioRxiv
Brain geometry matters in Alzheimer’s disease progression: a simulation study
M. Hoore, J. Kelling, M. Sayadmanesh, […] M. Meyer-Hermann

 

January 2020, bioRxiv
Sequential MAVS- and MyD88/TRIF-signaling triggers anti-viral responses of tick-borne encephalitis virus-infected murine astrocytes
L. Ghita, V. Breitkopf, F. Mulenge, […] I. Steffen, U. Kalinke

 

January 2020, eLife
Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models
L. S. Monasor, S. A. Müller, […] C. Haass, S. F. Lichtenthaler, S. Tahirovic

 

January 2020, J Exp Med
Pdap1 protects mature B lymphocytes from stress-induced cell death and promotes antibody gene diversification
V. Delgado-Benito, M. Berruezo-Llacuna, R. Altwasser, […] A. Akalin, M. Di Virgilio

 

January 2020, Frontiers in Immunology
Precision Medicine in Hymenoptera Venom Allergy: Diagnostics, Biomarkers, and Therapy of Different Endotypes and Phenotypes
S. Blank, J. Grosch, M. Ollert, M. B. Bilò

 

December 2019, Cell Rep
let-7 MicroRNAs Regulate Microglial Function and Suppress Glioma Growth through Toll-Like Receptor 7
A. BuonfiglioliI. E. Efe, D. Guneykaya, A. Ivanov, Y. Huang, […] D.H. Gutmann, M. Semtner, H. Kettenmann, S. Lehnardt

 

December 2019, J Hepatol
Hepatitis B virus-induced modulation of liver macrophage function promotes hepatocyte infection
S. Faure-Dupuy, M. Delphin, L. Aillot, L. Dimier, F. Lebossé, [...] M. Heikenwälder, D. Durantel, J. Lucifora

 

November 2019, The Neuroscientist
Amyloid, APP, and Electrical Activity of the Brain
D. Hefter, S. Ludewig, A. Draguhn, M. Korte

 

November 2019, BMC Med Genomics
Identification and ranking of recurrent neo-epitopes in cancer
E. Blanc, M. Holtgrewe, A. Dhamodaran, C. Messerschmidt, G. Willimsky, T. Blankenstein, D. Beule

 

November 2019, Neuron
Microglia/Brain Macrophages as Central Drivers of Brain Tumor Pathobiology
D. H. Gutmann, H. Kettenmann

 

October 2019, Nature Communications
Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology
J. K. Sonner, M. Keil, M. Falk-Paulsen, N. Mishra, A. Rehman, Kramer, [...] M. Platten

 

October 2019, JHEP Rep
Platelets in chronic liver disease, from bench to bedside
P. Ramadori, T. Klag, N. P. Malek, M. Heikenwälder

 

October 2019, Trends in Neurosciences
Cien Años de Microglía: Milestones in a Century of Microglial Research
A. Sierra, R. C. Paolicelli, H. Kettenmann

 

October 2019, Cell Reports
Injection of antibodies against immunodominant epitopes tunes germinal centres to generate broadly neutralizing antibodies
M. Meyer-Hermann

 

October 2019, Brain Behavior and Immunity
Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1
V. Haage, N. Elmadany , L. Roll, A. Faissner, D. H. Gutmann, M. Semtner, H. Kettenmann

 

October 2019, Cancer Res
Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology
X. Jiao, O. Nawab, T. Patel, A. V. Kossenkov, N. Halama, D. Jaeger, R. G. Pestell

 

October 2019, Cell Mol Life Sci
The role of polarisation of circulating tumour cells in cancer metastasis
M. Heikenwälder, A. Lorentzen

 

September 2019, Cell Reports
Efficient CRISPR/Cas9-Mediated Gene Knockin in Mouse Hematopoietic Stem and Progenitor Cells
N. T. Tran, T. Sommermann, R. Graf, J. Trombke, [...] K. Rajewsky, V. T. Chu

 

September 2019, Cancer Cell
Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention
T. O'Connor, X. Zhou, J. Kosla, A. Adili, M. G. Beccaria, […] U. Keller, M. Heikenwälder

 

September 2019, BMC Bioinformatics
SigsPack, a package for cancer mutational signatures
F. Schumann, E. Blanc, C. Messerschmidt, T. Blankenstein, A. Busse, D. Beule

 

August 2019, Allergy
Impaired memory B‐cell development and antibody maturation with a skewing toward IgE in patients with STAT3 hyper‐IgE syndrome
W. Veen, C. E. Krätz, C. I. McKenzie, P. M. Aui, J. Neumann, C. J. M. Noesel, [...], E. D. Renner

 

August 2019, Cell Reports
53BP1 Supports Immunoglobulin Class Switch Recombination Independently of Its DNA Double-Strand Break End Protection Function
D. Sundaravinayagam, A. Rahjouei, M. Andreani, D. Tupiņa, S. Balasubramanian, T. Saha, V. Delgado-Benito, V. Coralluzzo, O. Daumke, M. Di Virgilio

 

July 2019, Cancers (Basel)
An NF-kappaB- and IKK-Independent Function of NEMO Prevents Hepatocarcinogenesis by Suppressing Compensatory Liver Regeneration
C. Koppe, F. Reisinger, K. Wehr, M. Vucur, C. Trautwein, F. Tacke, M. Heikenwalder, T. Luedde

 

July 2019, Oncoimmunology
CCR5 status and metastatic progression in colorectal cancer
M. Suarez-Carmona, P. Chaorentong, J. N. Kather, R. Rothenheber, [...]  D. Jäger, I. Zoernig, N. Halama

 

July 2019, Nanomedicine
Preferential uptake of chitosan-coated PLGA nanoparticles by primary human antigen presenting cells
V. Durán, H. Yasar, J. Becker, D. Thiyagarajan, B. Loretz, U. Kalinke, C. M. Lehr

 

June 2019, Nature Communications
STING induces early IFN-β in the liver and constrains myeloid cell-mediated dissemination of murine cytomegalovirus
P.-K. Tegtmeyer, J. Spanier, K. Borst, J. Becker, A. Riedl, [...] U. Kalinke

 

April 2019, Cell Rep
Aryl Hydrocarbon Receptor Interacting Protein Maintains Germinal Center B Cells through Suppression of BCL6 Degradation
D. Sun, U. Stopka-Farooqui, S. Barry, E. Aksoy, G. Parsonage, A. Vossenkämper, M. Capasso, [...] O. Haworth

 

April 2019, Nature Medicine
Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer
M. Malehmir, D. Pfister, [...] A. Weber, M. Heikenwälder

 

April 2019, Leukemia
Intracellular expression of FLT3 in Purkinje cells: implications for adoptive T-cell therapies
N. Çakmak-Görür, J. Radke, S. Rhein, E. Schumann, G. Willimsky, F. L. Heppner, T. Blankenstein, A. Pezzutto

 

March 2019, Oncoimmunology
Localization-associated immune phenotypes of clonally expanded tumor-infiltrating T cells and distribution of their target antigens in rectal cancer
L. Penter, K. Dietze, J. Ritter, M. F. Lammoglia Cobo, J. Garmshausen, […] T. Blankenstein, M. Hummel, K. Dornmair, L. Hansmann

 

March 2019, Allergy
IL-4 receptor α blockade prevents sensitization and alters acute and long-lasting effects of allergen-specific immunotherapy of murine allergic asthma
D. Russkamp, A. Aguilar-Pimentel, [...] C. B. Schmidt-Weber, S. Blank

 

March 2019, Frontiers in Immunology
Discrepancies in the Tumor Microenvironment of Spontaneous and Orthotopic Murine Models of Pancreatic Cancer Uncover a New Immunostimulatory Phenotype for B Cells
S. Spear, J. B. Candido, [...] H. M. Kocher, M. Capasso

 

February 2019, Front Immunol
A Subset of CCL25-Induced Gut-Homing T Cells Affects Intestinal Immunity to Infection and Cancer
H. Fu, M. Jangani, A. Parmar, G. Wang, D. Coe, S. Spear, I. Sandrock, M. Capasso, [...] F. M. Marelli-Berg

 

February 2019, Science
BCR-dependent lineage plasticity in mature B cells
R. Graf, J. Seagal, K.L. Otipoby, K.P. Lam, S. Ayoub, B. Zhang, S. Sander, V.T. Chu, K. Rajewsky

 

February 2019, Cell Reports
Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation
G. Garg, A. Muschaweckh, H. Moreno, A. Vasanthakumar, S. Floess, [...] J. Huehn, A. Kallies, T. Korn

 

January 2019, Acta Neuropathol Commun
Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes/macrophages in health and glioma
V. Haage, M. Semtner, R. Oliveira Vidal, D. Perez Hernandez, W. W. Pong, […] H. Kettenmann, D.H. Gutmann

 

January 2019, J Clin Invest
Effective NY-ESO-1-specific MHC II-restricted T cell receptors from antigen-negative hosts enhance tumor regression
L. Poncette X. Chen, F. K. M. Lorenz, T. Blankenstein

 

January 2019, Neural Plasticity
Immune Challenge Alters Reactivity of Hippocampal Noradrenergic System in Prenatally Stressed Aged Mice
G. Grigoryan, N. Lonnemann, M. Korte

 

January 2019, Nature Neuroscience
Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
S. Parhizkar, T. Arzberger, [...] C. Haass

 

November 2018, Progress in Biophysics and Molecular Biology
PK/PD-based adaptive tailoring of oseltamivir doses to treat within-host influenza viral infections
G. Montaseri, A. Boianelli, E. A. Hernandez-Vargas, M. Meyer-Hermann

 

November 2018, Brain Behav Immun
Microglia have a protective role in viral encephalitis-induced seizure development and hippocampal damage
I. Waltl, C. Käufer, [...] U. Kalinke, W. Löscher

 

October 2018, Nature Communications
The olfactory epithelium as a port of entry in neonatal neurolisteriosis
D. Pägelow, C. Chhatbar, A. Beineke, X. Liu, [...] U. Kalinke, R. Förster, S. Halle, P. Valentin-Weigand, M. W. Hornef, M. Fulde

 

October 2018, Cell Reports
Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis
C. Chhatbar, C. N. Detje, E. Grabski, K. Borst, J. Spanier, L. Ghita, [...] , U. Kalinke

 

October 2018, Front Cell Neurosci
IFN-γ Producing Th1 Cells Induce Different Transcriptional Profiles in Microglia and Astrocytes
C. K. Prajeeth, O. Dittrich-Breiholz, S. R. Talbot, P. A. Robert, J. Huehn, M. Stange

 

September 2018, Frontiers in Immunology
Computer Simulation of Multi-Color Brainbow Staining and Clonal Evolution of B Cells in Germinal Centers
M. Meyer-Hermann, S. C. Binder, L. Mesin, G. D. Victora

 

September 2018, PNAS
Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures
C. Käufer, C. Chhatbar, [...] U. Kalinke, W. Löscher

 

August 2018, Cell Rep
Transcriptional and Translational Differences of Microglia from Male and Female Brains
D. Guneykaya, A. Ivanov, D. Perez Hernandez, V. Haage, B. Wojtas, N. Meyer, […]  H. Kettenmann, S. A. Wolf

 

August 2018, Plos Pathogens
Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice
W. Koestner, J. Spanier, [...] F. Wacker, U. Kalinke

 

August 2018, Mol Ther
CAR T Cells with Enhanced Sensitivity to B Cell Maturation Antigen for the Targeting of B Cell Non-Hodgkin's Lymphoma and Multiple Myeloma
J. Bluhm, E. Kieback, S.F. Marino, F. Oden, J. Westermann, M. Chmielewski, H. Abken, W. Uckert, U.E. Höpken, A. Rehm

 

July 2018, Nat. Med
Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate
L. Bunse, S. Pusch, [...] W. Wick, M. Platten

 

April 2018, J Hepatol
Type I interferon receptor signaling delays Kupffer cell replenishment during acute fulminant viral hepatitis
K. Borst, T. Frenz, [...] M. Heikenwälder, G. Sutter, U. Kalinke

 

February 2018, Neural Regen Res
Regulation of neuroinflammatory properties of glial cells by T cell effector molecules
C. K. Prajeeth, J. Huehn, M. Stange

immune-system-1132182_1920

Funding period

Nov. 2017 – Dec. 2021

 

Funding amount

6,000,000 € from the Initiative and Networking Fund of the Helmholtz Association

5,000,000 € co-funding by the Research Centers

 

Participating Helmholtz Centers

German Cancer Research Center (DKFZ)
German Center for Neurodegenerative Diseases (DZNE)
Helmholtz Center Munich (HMGU)
Helmholtz Center for Infection Research (HZI)
Max Delbrück Center for Molecular Medicine (MDC)

 

Coordination

MDC

 

Governing Body

Klaus Rajewsky (MDC)
Michela Di Virgilio (MDC)
Mathias Heikenwälder (DKFZ)
Michael Heneka (DZNE)
Ulrich Kalinke (HZI)
Claudia Traidl-Hoffmann (HMGU)

 

Contact

 

Governing Body

Michela Di Virgilio
Michela.DiVirgilio@mdc-berlin.de

Klaus Rajewsky
Klaus.Rajewsky@mdc-berlin.de


Coordination

Charlotte Quirin
Charlotte.Quirin@mdc-berlin.de
+49 30 9406 1648

Nadja Oellrich
Nadja.Oellrich@mdc-berlin.de

 

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