Ronchi Lab

Host-Microbiota Interactions

Prof. Dr. Francesca Ronchi
Prof. Dr. Francesca Ronchi
PI Host-Microbiota Interactions

francesca.ronchi(at)charite.de

+49 30 450 524124

Project

Over the past decade, it has become clear that the intestinal microbiota can affect host metabolism and systemic immune cell responses also in distal organs, such as the Central Nervous System (CNS), through the dissemination of bacterial products or metabolites, which strongly depend on the substrates available through dietary intake. Nutrition became a complementary, alternative and successful approach in the management of metabolic and neurological conditions. However, for this to be effective for many more patients we lack an adequate understanding of the exact mechanisms involved in the diet-intestinal microbiota-mediated CNS effects.

We and others showed that bacteria and diets influence the host immune response, however how exactly the diet-microbiota interplay can affect the functions of the immune cells residing and homing to the CNS, during healthy and inflammatory conditions, remains poorly understood.

Our lab aims to study the cellular and molecular mechanisms of how diets affect the composition and function of the gut microbiota and, subsequently, the CNS functions under healthy and neurological disease conditions, such as multiple sclerosis, refractory epilepsy and Alzheimer’s disease. To address our goals we combine state-of-the-art next generation ‘OMICs techniques and gnotobiology techniques in animal models.

We are also interested in studying the microbiota role in the pathogenesis of inflammatory bowel disease (IBD) and how innate immune pathways, such as inflammasome, contribute to intestinal homeostasis and during intestinal inflammation.

Lab Members

Dr. Laura Díaz Marugan
Dr. Laura Díaz Marugan
Postdoc

laura.diaz(at)charite.de

Andrina Rutsch
Andrina Rutsch
PhD Student

andrina.rutsch(at)charite.de

Johan Kantsjö
Johan Kantsjö
PhD Student

johan.kantsjoe(at)charite.de

Publications

1. Rutsch A, Kantsjö JB, Ronchi F*, *corresponding author
Frontiers in Immunol., 2020:11,3237
2020
2. Gil-Cruz C, Perez-Shibayama C, De Martin A, Ronchi F, van der Borght K, Niederer R, Onder L, Lütge M, Novkovic M, Nindl V, Ramos G, Arnoldini M, Slack EMC, Boivin-Jahns V, Jahns R, Wyss M, Mooser C, Lambrecht BN, Maeder MT, Rickli H, Flatz L, Eriksson U, Geuking MB, McCoy KD, Ludewig B.
Science, 2019:366(6467):881-886.
2019
3. Iannone LF, Preda A, Blottière HM, Clarke G, Albani D, Belcastro V, Carotenuto M, Cattaneo A, Citraro R, Ferraris C, Ronchi F, Luongo G, Santocchi E, Guiducci L, Baldelli P, Iannetti P, Pedersen S, Petretto A, Provasi S, Selmer K, Spalice A, Tagliabue A, Verrotti A, Segata N, Zimmermann J, Minetti C, Mainardi P, Giordano C, Sisodiya S, Zara F, Russo E , Striano P
Expert Review of Neurotherapeutics, 19:10, 1037-1050
2019
4. Hebbandi Nanjundappa R*, Ronchi F*, Wang J, Clemente-Casares X, Yamanouchi J, Umeshappa C, Yang Y, Blanco J, Bassolas H, Salas A, Serra P, Slattery RM, Mooser C, Wyss M, Macpherson AJ, McKay DM, McCoy KD**, Santamaria P**, *shared first-authors, ** shared last-authors
Cell, 171(3):655-667.e17
2017
5. Mamantopoulos M*, Ronchi F*, Van Hauwermeiren F, Vieira-Silva S, Yilmaz B, Martens L, Saeys Y, Drexler SK, Yazdi AS, Raes J, Lamkanfi M, McCoy KD**, Wullaert A**, *shared first-authors, **shared last-authors
Immunity, 47(2):339-348.e4
2017
6. Ronchi F*, Basso C*, Preite S, Reboldi A, Baumjohann D, Perlini L, Lanzavecchia A, Sallusto F., *shared first-authors
Nat Commun., 7:11541
2016

Neumann Lab

Lymphocyte Biology and Microenvironment

Dr. Christian Neumann
Dr. Christian Neumann
Principal Investigator

+49 (0)30 450 524 232

Projects

Tissue Adaptation Of Innate And Adaptive Lymphoid Cells

Chronically stimulated surfaces of the body, in particular the gastrointestinal tract (GI), are major sites where immune cells traffic and reside. Because mucosal surfaces are constantly challenged by fluctuating environmental perturbations, immune cells at these sites display a remarkable adaptive capacity in order to fend off microbial challenges and safeguard organ homeostasis. Tissue-resident innate lymphoid cells (ILC) and adaptive T helper cells are key players in protecting mucosal surfaces and maintaining immune homeostasis. To fulfil this delicate job, is has become clear that mucosal lymphocytes differ significantly in phenotype and function from their circulating or lymphoid-organ counterparts.

The Neumann lab is interested in the molecular basis of lymphocyte adaption to mucosal organs. The goal of our research is to understand the genetic, epigenetic and transcriptional mechanisms that determine the tissue-specific functions of distinct lymphocyte populations. Furthermore, we aim to identity the specific (micro)environmental cues that trigger tissue adaptation and how they influence each particular step of lymphocyte differentiation and lineage commitment.

 

Host – Microbiota Interactions In Health And Disease

The GI tract constitutes the largest interface between the host and the environment. Inhabited by a plethora of microorganisms (termed microbiota), the GI tract is enriched for immune cells that engage in a complex dialogue with the microbiota to maintain a state of homeostasis that is mutually beneficial. On one side, microbiota and products thereof are indispensable for shaping the development and function of the host immune system, thereby exerting multifaceted impacts on gut and systemic health. On the other side, intestinal immune cells control the composition of microbial communities, promoting colonization with mutualistic microbes and neutralization of invasive pathogens. Importantly, any imbalance of this physiological equilibrium precipitates a pathological state known as gut dysbiosis that has been linked to a variety of intestinal but also extraintestinal diseases, such as inflammatory bowel diseases, autoimmunity and metabolic disorders.

Therefore, we believe that deciphering the molecular underpinnings of the intimate cross talk between host and microbiota during homeostasis and dysbiosis may hold the key to understand many idiopathic diseases. Our research is focused on gut-resident innate and adaptive lymphocytes that specifically control host-microbiota symbiosis. Vice versa, we are interested in the ability of certain microbes to shape and heighten tissue immunity. In addition, a major focus of our research lies on the role of intestinal epithelial cells as the primary interface between host tissue and microbiota that facilitates the bidirectional communication between immune system and microbiota.

Twitter Account: https://twitter.com/lab_neumann

4e_1_x1000
Transmission electron microscopy (TEM) of murine colonic epithelial cells and luminal bacteria. © Neumann Lab
Immunostaining of the transcription factor c-Maf (magenta) and DAPI (green) in the murine small intestinal epithelium. The image highlights the zonated expression of c-Maf in the mid-villus region, where it regulates enterocyte differentiation and function. © Neumann Lab
Immunostaining of murine small intestinal organoids. Epithelial cells are stained with EpCAM (green), cell nuclei with DAPI (blue) and Paneth cells with lysozyme (red). © Neumann Lab
Immunostaining of colonic cross-sections of mice naturally infected with opportunistic worms. Cell nuclei are stainind with DAPI (blue), Goblet cells and mucus with UEA-1 (green) and worms are visible via autofluorescence (red). © Neumann Lab
1a_3
Transmission electron microscopy (TEM) of murine colonic epithelial cells and luminal bacteria. © Neumann Lab
Immunostaining of PEPT1 (red), a peptide transporter, which is strongly regulated by the transcription factor c-Maf in the murine small intestinal epithelium. Epithelial cells are stained with EpCAM (green) and cell nuclei with DAPI (blue). © Neumann Lab
Immunostaining of murine small intestinal organoids. Epithelial cells are stained with EpCAM (green), cell nuclei with DAPI (grey) and Paneth cells with lysozyme (red). © Neumann Lab
Immunostaining of colonic cross-sections of mice naturally infected with opportunistic worms. Cell nuclei are stainind with DAPI (blue), Goblet cells and mucus with UEA-1 (green) and worms are visible via autofluorescence (red). © Neumann Lab

Recent Findings

Molecular regulation of enterocyte differentiation and intestinal nutrient uptake

Throughout the last years it has become increasingly clear that the intestinal epithelium has a remarkable capacity to dynamically adapt to environmental changes, such as alterations of the microbiota, in response to inflammation, injury or variations in energy supply and demand. This plasticity, which has been coined epithelial remodelling, is characterized by a coordinated reshaping of the intestinal epithelial structure and function to appropriately respond to changing environmental input and to eventually restore homeostasis. Especially, the critical importance of intestinal plasticity for maintaining energy balance of the whole organism has been highlighted, yet the molecular mechanisms and transcriptional mediators governing enterocytes and epithelial nutritional remodelling have remained incompletely defined. 

We recently identified c-Maf as a novel key transcriptional regulator of small intestinal enterocytes (Cosovanu et al., JEM 2022). c-Maf, whose expression is determined by opposing Noggin/BMP signals, critically controls the differentiation and function of enterocytes, especially their capacity to sense and take up nutrients. Importantly, the epithelial cell-specific deletion of c-Maf not only compromises the organismal metabolic and nutritional status (due to defects in intestinal nutrient uptake), but also affects the abundance of intraepithelial lymphocytes and commensal epithelial cell-attaching Segmented Filamentous Bacteria, highlighting the close interdependence between intestinal epithelial cell function, the intestinal immune system and microbiota.

Currently, we are studying the role of epithelial c-Maf in experimental models of intestinal remodelling and inflammation, in which nutrient sensing and absorption are dynamically regulated and/or pathologically altered. In addition, we are determining the translational relevance of our murine studies by assessing c-Maf expression and function in human enterocytes in health and intestinal inflammation.

Pubmed: https://pubmed.ncbi.nlm.nih.gov/36121416/

Balancing the gut – How the immune system maintains a healthy gut microbiota

We recently uncovered a critical mechanism that controls immune reactions against intestinal microorganisms (Neumann et al., Nature Immunology 2019). By focussing on so-called regulatory T cells (Treg), which prevent harmless microorganisms in the intestine from being attacked by the immune system, we identified a transcription factor, c-Maf, to be critical for the development and function of specific Treg cells in the gut. Deletion of c-Maf in Treg cells resulted in uncontrolled intestinal immunity to the microbiota and a profound microbial dysbiosis. The change in microbiota composition proved remarkably stable. When we transferred the altered microbiota to mice with intact c-Maf-dependent Treg cells, we similarly observed an overreaction of the intestinal immune system, indicating that both the immune system and the microbiota mutually contribute to establishing and maintaining a balanced host-microbiota relationship.

In summary, these findings could explain how microbial dysbiosis can contribute to chronic inflammatory bowel diseases. The identification of c-Maf as a key factor employed by the intestinal immune system to maintain a healthy microbiota, as well as of the signals regulating its expression, represent novel intervention points to counteract microbial dysbiosis and to re-establish intestinal immune homeostasis.

This work was done in close cooperation with Dr Sascha Rutz (Genentech, San Francisco), Dr Axel Kallies (University of Melbourne and Walter and Eliza Hall Institute of Medical Research, Melbourne) and Dr Alexander Scheffold (Kiel University and University Medical Center-UKSH, Kiel)    

Press release: https://www.charite.de/en/service/press_reports/artikel/detail/alles_im_gleichgewicht/

Pubmed: https://pubmed.ncbi.nlm.nih.gov/30778241/

Lab Members

Catalina Cosovanu
Catalina Cosovanu
PhD student

catalina.cosovanu(at)charite.de

+49 (0)30 450 524 039

Jacopo Ulisse
Jacopo Ulisse
PhD student

+49 (0)30 450 524 039

Abarajitha Ramesh
Abarajitha Ramesh
PhD student

Cerys Ann Fisher
Cerys Ann Fisher
Research Assistant

+49 (0)30 450 524 047

Publications

Chang Y, Bach L, Hasiuk M, Wen L, Elmzzahi T, Tsui C, Gutiérrez-Melo N, Steffen T, Utzschneider DT, Raj T, Jost PJ, Heink S, Cheng J, Burton OT, Zeiträg J, Alterauge D, Dahlström F, Becker JC, Kastl M, Symeonidis K, van Uelft M, Becker M, Reschke S, Krebs S, Blum H, Abdullah Z, Paeschke K, Ohnmacht C, Neumann C, Liston A, Meissner F, Korn T, Hasenauer J, Heissmeyer V, Beyer M, Kallies A, Jeker LT, Baumjohann D. TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf. Sci Immunol. 2024 Mar

Cosovanu C, Resch P,  Jordan S,  Lehmann A, Ralser M, Farztdinov V, Spranger J, Mülleder M, Brachs S, Neumann C. Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice. J Exp Med. 2022 Dec

Ahlers J, Mantei A, Lozza L, Stäber M, Heinrich F, Bacher P, Hohnstein T, Menzel L, Yüz SG, Alvarez-Simon D, Bickenbach AR, Weidinger C, Mockel-Tenbrinck N, Kühl AA, Siegmund B, Maul J, Neumann C*, Scheffold A*. A Notch/STAT3-driven Blimp-1/c-Maf-dependent molecular switch induces IL-10 expression in human CD4+ T cells and is defective in Crohn´s disease patients. Mucosal Immunol. 2022 Mar

*Equal contribution

Cosovanu C and Neumann C. The Many Functions of Foxp3+ Regulatory T Cells in the Intestine. Front. Immunol. 2020 Oct

Tizian C, Lahmann A, Hölsken O, Cosovanu C, Kofoed-Branzk M, Heinrich F, Mashreghi MF, Kruglov A, Diefenbach A, Neumann C. c-Maf restrains T-bet-driven programming of CCR6-negative group 3 innate lymphoid cells. Elife. 2020 Feb

Neumann C, Scheffold A, Rutz S. Functions and regulation of T cell-derived interleukin-10. Semin Immunol. 2019 Aug

Neumann C, Blume J, Roy U, Teh PP, Vasanthakumar A, Beller A, Liao Y, Heinrich F, Arenzana TL, Hackney JA, Eidenschenk C, Gálvez EJC, Stehle C, Heinz GA, Maschmeyer P, Sidwell T, Hu Y, Amsen D, Romagnani C, Chang HD, Kruglov A, Mashreghi MF, Shi W, Strowig T, Rutz S, Kallies A, Scheffold A. c-Maf-dependent Treg cell control of intestinal Th17 cells and IgA establishes host-microbiota homeostasis. Nat Immunol. 2019 Apr

Ekmekciu I, von Klitzing E, Neumann C, Bacher P, Scheffold A, Bereswill S, Heimesaat MM. Front MFecal Microbiota Transplantation, Commensal Escherichia coli and Lactobacillus johnsonii Strains Differentially Restore Intestinal and Systemic Adaptive Immune Cell Populations Following Broad-spectrum Antibiotic Treatment. Front Microbiol. 2017 Dec

Ekmekciu I, von Klitzing E, Fiebiger U, Neumann C, Bacher P, Scheffold A, Bereswill S, Heimesaat MM. The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment. Front Cell Infect Microbiol. 2017 May

Ekmekciu I, von Klitzing E, Fiebiger U, Escher U, Neumann C, Bacher P, Scheffold A, Kühl AA, Bereswill S, Heimesaat MM. Immune Responses to Broad-Spectrum Antibiotic Treatment and Fecal Microbiota Transplantation in Mice. Front Immunol. 2017 Apr

Neumann K, Rudolph C, Neumann C, Janke M, Amsen D, Scheffold A. Liver sinusoidal endothelial cells induce immunosuppressive IL-10-producing Th1 cells via the Notch pathway. Eur J Immunol. 2015 Jul

Haftmann C, Stittrich AB, Zimmermann J, Fang Z, Hradilkova K, Bardua M, Westendorf K, Heinz GA, Riedel R, Siede J, Lehmann K, Weinberger EE, Zimmel D, Lauer U, Häupl T, Sieper J, Backhaus M, Neumann C, Hoffmann U, Porstner M, Chen W, Grün JR, Baumgrass R, Matz M, Löhning M, Scheffold A, Wittmann J, Chang HD, Rajewsky N, Jäck HM, Radbruch A, Mashreghi MF. miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim. Eur J Immunol. 2015 Apr

Neumann C, Heinrich F, Neumann K, Junghans V, Mashreghi MF, Ahlers J, Janke M, Rudolph C, Mockel-Tenbrinck N, Kühl AA, Heimesaat MM, Esser C, Im SH, Radbruch A, Rutz S, Scheffold A. Role of Blimp-1 in programing Th effector cells into IL-10 producers. J Exp Med. 2014 Aug

Neumann C, Scheffold A. Therapeutische Manipulation entzündungsfördernder T-Zellen : Von Suppression zur Selbstkontrolle [Therapeutic manipulation of inflammation-promoting T cells: from suppression to self-control]. Z Rheumatol. 2013 Sep

Ni Choileain S, Weyand NJ, Neumann C, Thomas J, So M, Astier AL. The dynamic processing of CD46 intracellular domains provides a molecular rheostat for T cell activation. PLoS One. 2011 Jan

Jordan Lab

Laboratory of Microbiology, Metabolism & Inflammation (LoMMI)

Projects

Current research

What we eat affects our immune system. High calorie diets as they are typical in the western world cause systemic low-grade chronic inflammation contributing to many diseases including metabolic, cardiovascular and autoimmune disorders. In contrast, reduced calorie intake and fasting regimens are associated with improved outcomes for numerous diseases including cardiovascular disease, type 2 diabetes mellitus, non-alcoholic fatty liver diseases (NAFLD), asthma, psoriasis, rheumatoid arthritis and multiple sclerosis. In addition, caloric restriction has been proven to extend the healthy lifespan of many organisms.

The microorganisms that live in our intestines participate in the digestion of food and play an important role in the control of our immune system.

The goal of our research is to understand the cellular and molecular mechanisms that link our gut bacteria to calorie intake and systemic inflammation. To this aim, we combine cutting-edge technologies in the fields of microbiome research, metabolism research and immunology. Our vision is to develop innovative therapies for the prevention and treatment of widespread chronic inflammatory diseases affecting millions of patients worldwide.

Recent findings

We investigated the effect of fasting on cells of the immune system. Fasting reduced the numbers of monocytes in the blood circulation of mice and healthy humans. Monocytes are immune cells that play an important role in the initiation and maintenance of inflammation. Therefore, fasting might reduce the risk to develop inflammatory diseases.

Furthermore, fasting reduced the inflammatory activity of monocytes in a model of human multiple sclerosis and greatly improved the clinical course of the disease. Importantly, while fasting improved inflammatory disease outcome, it did not compromise the immune response during an acute infection (Jordan et al., Cell 2019).

Design by Wiegand von Hartmann GbR

Lab Members

Dr. Stefan Jordan
Dr. Stefan Jordan
PI Microbiology, Metabolism & Inflammation

stefan.jordan(at)charite.de

+49 (030) 450 524368

INTERACTIONS

 

We are convinced that collaboration is a driving force of scientific advancement. Research activities at the Institute of Microbiology, Infectious Diseases and Immunology at Charité – Universitätsmedizin Berlin are focused on microbial and environmental factors controlling the immune system. All research groups are located on the same floor, share laboratory space and a large lunch room creating a unique atmosphere of interaction and collaboration among PIs and trainees. We have joint labmeetings on a regular basis, a weekly journal club followed by a happy hour, and we invite international guests for presentations and discussions. The Jordan Lab / LoMMI develops joint research projects with the groups of Claudia Duerr, Christoph Klose, Melanie Conrad, Stefan Bereswill / Markus Heimesaat, Christian Neumann and Andreas Diefenbach, works closely together with groups at Charité – Universitätsmedizin Berlin and other institutions in Berlin and Brandenburg, and collaborates with national and international partners.

Contact us!

If you are interested in joining our team, contact us! We are always looking for passionate researchers (interns, Master’s or doctorate students and Postdoctoral fellows).

Send your CV or resume and cover letter to stefan.jordan[at]charite.de

Publications

Funding

DFG Priority Programme 1937 “Innate Lymphoid Cells”

Follow us on Twitter

@immunodiet: Latest scientific facts concerning dietary effects on the immune system.

@jordan_LoMMI: News from the Jordan Lab.

Tissue Monitoring by Macrophages

Tissue Monitoring by Macrophages

Dr. Stathis Stamatiades
Dr. Stathis Stamatiades
Principal Investigator

Research Interests

Tissue resident macrophages are evolutionary old, tissue resident myeloid cells, found from invertebrates (e.g. D. melanogaster) to higher mammals (e.g. Homo sapiens). They are phagocytic cells and are generally characterised as tissue sentinels against invading pathogens. Yet, macrophages are far more than just bug-eaters! They actually have important roles in tissue homeostasis. We are generally interested to understand the functions of macrophages at steady state and in disease and how they regulate tissue homeostasis.

Elie Metchnikoff first described phagocytes (i.e. macrophages) more than a century ago in the star fish larvae as cells that fight against invading pathogens and as regulators of tissue homeostasis. Although, nowadays, the development of tissue resident macrophages has been extensively studied, their in situ functions are unclear and need to be better defined. In our endeavour to understand the role of macrophages within a specific tissue, we seek to answer six simple, yet, important, questions: Who? What? When? Where? Why? How?

Answering these fundamental questions will help us shed some light on the fascinating world of macrophages!

Research Methods

We employ a plethora of research techniques to study macrophages e.g. flow cytometry and gene expression. Since it is impossible to understand the biology of macrophages using cell lines or in vitro, we rely heavily on in vivo models. Importantly, we strongly believe that appropriate localisation of cell populations within their natural tissue setting is critical for relating cell diversity to function. Therefore, in order to answers our scientific questions, we are very keen on using state of the art imaging techniques: e.g. immunofluorescence (IF) microscopy, whole mount with tissue clearing, intravital microscopy, and transmission electron microscopy (TEM). If you are interested to see some representative pics and videos of our work, do have a look at our gallery!

Gallery – Seeing is believing

Snapshots

Movies

In vivo imaging of the renal cortex of a Cxc3r1gfp/+ mouse. The vasculature was labeled with i.v. injection of TRITC-Dextran. From Stamatiades et. al. Cell, 2016.

Probing of the tissue by macrophages (green) in the renal cortex of a Cxc3r1gfp/+ mouse. The vasculature was labeled with i.v. injection of TRITC-Dextran. From Stamatiades et. al. Cell, 2016.

Phagocytosis of beads by monocytes. From Carlin, Stamatiades et. al. Cell, 2013.

In vivo labeling of neutrophils. Carlin, Stamatiades et. al. Cell, 2013.

In vivo labeling of monocytes and neutrophils. Carlin, Stamatiades et. al. Cell, 2013.

Take up of immunce complexes (IC, red) by a kidney macrophage.

Uptake of ovalbumin in the liver.

3D rendering of a IC-loaded (red) kidney macrophage to demonstrate that IC are inside the macrophage.

Phagocytosis of M. marinum by a kidney macrophage. From Stamatiades et. al. Cell, 2016.

In vivo imaging of the glomerulus in a Cxc3r1gfp/+ mouse. The vasculature was labeled with i.v. injection of TRITC-Dextran.

In vivo imaging of a large blood vessel in the kidney of a Cxc3r1gfp/+ mouse. The vasculature was labeled with i.v. injection of TRITC-Dextran.

Phagocytosis of C. albicans by a kidney macrophage. From Stamatiades et. al. Cell, 2016.

Phagocytosis of 20 nm beads by a kidney macrophage. From Stamatiades et. al. Cell, 2016.

Knowledge sharing

Because science is all about sharing, we share any ‘expertise’ we have acquired and developed. To this, we regularly review online good antibodies for IF microscopy, in order to make IF less stressful for other colleagues: https://www.biocompare.com/General-Search/?search=stamatiades

Projects

The role of myeloid cells in immune complex-driven nephritis

Immune complexes (IC)-mediated pathologies (also known as type III hypersensitivity reactions) affect millions worldwide, with a very high socioeconomic burden. Type III hypersensitivity frequently targets the kidney, causing inflammation, which could progress to end stage renal failure and the need for dialysis or transplantation. The current therapeutic interventions for IC-mediated nephritis are costly, non-specific and come with severe side effects. A better understanding of the mechanistic underpinnings of the disease is needed, in order to build new, more specific treatments.

Myeloid cell infiltration is one of the most striking features of renal inflammation caused by IC and it correlates with poor patient prognosis. Our published work has shown that the macrophages that reside in the renal interstitium, termed kidney-resident macrophages (krMΦs), initiate type III hypersensitivity in the kidney, by scavenging circulating IC that are pumped into the renal interstitium by endothelial cells.

Our findings provide a simple model to explain how IC cause kidney inflammation. Yet, despite this progress, the underlying mechanisms that lead to IC-mediated tissue injury remain unclear. We aim to delineate the role of different subsets of myeloid cells in IC-driven inflammation in the kidney. Thus, our work has the potential to discover novel pathways that can be further harnessed for the prevention of type III hypersensitivity.

Team

Olivia Hochleitner
Olivia Hochleitner
Erasmus BSc student
Kama Atretkhany, Ph.D.
Kama Atretkhany, Ph.D.
Postdoc

Contact us

If you have a passion about science, are interested in our work and would like to join us, get in touch! We are always looking for postdocs, students or interns. Send your CV and cover letter with your research interests to stamatiadeslab[at]gmail.com.

Publications (*equal contribution)

 

Kansler ER, Dadi S, Krishna C, Nixon BG, Stamatiades EG, Liu M, Kuo F, Zhang J, Zhang X, Capistrano K, Blum KA, Weiss K, Kedl RM, Cui G, Ikuta K, Chan TA, Leslie CS, Hakimi AA, Li MO (2022). Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies. Nat Immunol. May 26. doi: 10.1038/s41590-022-01213-2. Epub ahead of print.

Chou C, Zhang X, Krishna C, Nixon BG, Dadi S, Capistrano KJ, Kansler ER, Steele M, Han J, Shyu A, Zhang J, Stamatiades EG, Liu M, Li S, Do MH, Edwards C, Kang DS, Chen CT, Wei IH, Pappou EP, Weiser MR, Garcia-Aguilar J, Smith JJ, Leslie CS, Li MO (2022). Programme of self-reactive innate-like T cell-mediated cancer immunity. Nature; 605:139-145.

Feng* Y, Dionne* MS, Stamatiades* EG, Kierdorf* K (2021). Deciphering phagocyte functions across different species. Front. Cell Dev. Biol; 9:712929.

Xu K, Yin N, Peng M, Stamatiades EG, Chhangawala S, Shyu A, Li P, Zhang X, Do MH, Capistrano KJ, Chou C, Leslie CS, Li MO (2021). Glycolytic ATP fuels phosphoinositide 3-kinase signaling to support effector T helper 17 cell responses. Immunity; 54:976-987.

Xu K, Yin N, Peng M, Stamatiades EG, Shyu A, Li P, Zhang X, Do MH, Wang Z, Capistrano KJ, Chou C, Levine AG, Rudensky AY, Li MO (2021). Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity. Science; 371:405-410.

Liu M, Kuo F, Capistrano KJ, Kang D, Nixon BG, Shi W, Chou C, Do MH, Stamatiades EG, Gao S, Li S, Chen Y, Hsieh JJ, Hakimi AA, Taniuchi I, Chan TA, Li MO (2020). TGF-β suppresses type 2 immunity to cancer. Nature; 587:115-120.

Li S, Liu M, Do MH, Chou C, Stamatiades EG, Nixon BG, Shi W, Zhang X, Li P, Gao S, Capistrano KJ, Xu H, Cheung NV, Li MO (2020). Cancer immunotherapy via targeted TGF-β signalling blockade in TH cells. Nature; 587:121-125.

Berrien-Elliott MM, Sun Y, Neal C, Ireland A, Trissal MC, Sullivan RP, Wagner JA, Leong JW, Wong P, Mah-Som AY, Wong TN, Schappe T, Keppel CR, Cortez VS, Stamatiades EG, Li MO, Colonna M, Link DC, French AR, Cooper MA, Wang WL, Boldin MP, Reddy P, Fehniger TA (2019). MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells. Immunity; 51:479-490.

Stamatiades EG, Li MO (2019). Tissue Resident Cytotoxic Innate Lymphoid Cells in Tumour Immunosurveillance. Seminars in Immunology; 41:101269

Stamatiades EG, Tremblay ME, Bohm M, Crozet L, Bisht K, Kao D, Coelho C, Fan Xi, Yewdell WT, Davidson A, Heeger PS, Diebold S, Nimmerjahn F, Geissmann F (2016). Immune Monitoring Of Trans-Endothelial Transport By Kidney Resident Macrophages. Cell; 166:991-1003.

Carlin* LM, Stamatiades* EG, Auffray C, Hanna RN, Glover L, Vizcay-Barrena G, Hedrick CC, Cook HT, Diebold S, Geissmann F (2013). Nr4a1-Dependent Ly6Clow Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal. Cell; 153: 362-75.

Funding

Triantafyllopoulou Lab

Innate Immunity In Rheumatic Diseases

Projects

Lab Members

Publications

Moter Lab

Biofilmcenter

Our main research interest is to develop novel tools for detection and therapy of biofilm-associated microbial infections, in particular for the in situ analysis of biofilm growth and bacteria-host interactions. These tools will aid to identify bacterial species or structures as targets for innovative diagnostic and therapeutic approaches, as well as to determine the efficacy of antimicrobial agents on biofilm microbes. Currently, we focus on the spatial organization of the oral and gut microbiome and the interaction with the host. Further projects deal with understanding of infections due to fastidious or yet uncultured microorganisms.

PD Dr. Annette Moter, MD PhD
PD Dr. Annette Moter, MD PhD
PI Biofilmcenter

annette.moter(at)charite.de

+49 (0)30 450 524 226

Projects

1. Microbial biofilms

– Analysis of composition and activity of microbial biofilms in the clinical setting

– Diagnostics in biofilm-associated infections such as Infective Endocarditis, cardiovascular devices, oral biofilms in periodontitis and peri-implantitis, wounds and others

 

2. Testing of antimicrobial surfaces and antifouling materials against microbial biofilms in vitro, in vivo and ex vivo

– Measuring the efficacy of antimicrobial surfaces and antimicrobial materials against biofilms by FISH

 

3. Fluorescence in situ hybridization (FISH) and molecular analysis tools

– Combining FISH and nucleic acid amplification techniques (PCR, real-time PCR, NGS) for

  • Quantity and distribution of the microorganisms
  • Identification of key players and key pathogens
  • Study the mucosal interfaces
  • Development of FISH for the diagnostic setting

 

4. Whipple’s Disease and Tropheryma whipplei

– Consultant Laboratory for Tropheryma whipplei appointed by Robert Koch-Institute (RKI) 

For more information, see http://www.moter-diagnostics.com/

 

5. Culture negative infections and fastidious organisms

– Human Intestinal Spirochetosis

– Chorioamnionitis

Lab Members

Laura Kursawe
Laura Kursawe
Research Assistant

laura.kursawe(at)charite.de

Gitina Fiedler
Gitina Fiedler
Technichian

gitina.fiedler(at)charite.de

Julia Schmidt
Julia Schmidt
Research Assistant

julia.schmidt2(at)charite.de

+49 (0)30 450 524 524 (office)

+49 (0)30 450 524 015 (lab)

Alexandra Wießner
Alexandra Wießner
Research Assistant

alexandra.wiessner(at)charite.de

+49 (0)30 450 524 524

+49 (0)30 450 524 015

Dr. Judith Kikhney
Dr. Judith Kikhney
Postdoc

judith.kikhney(at)charite.de

+49 (0)30 450 524 524

+49 (0)30 450 524 006

Funding

The European Union (EU) and the European Regional Development Fund (EFRE) support our research. Aim of our ProFIT project is to increase the sensitivity of FISH. Ultimate goal is to test antimicrobial substances or surfaces in a FISH biofilm test-platform for improved medical implants. Biofilmzentrum carries out the project in cooperation with the SME MoKi Analytics. For more information, see http://www.moki-analytics.com/

We are also supported by the Bundesministerium für Bildung und Forschung, the Bundesministerium für Wirtschaft und Energie and the EXIST program.

Publications

Conrad Lab

Reproductive Immunology

Dr. Melanie Conrad
Dr. Melanie Conrad
PI Reproductive Immunology

melanie.conrad(at)charite.de

+49 (0)30 450 524 232

Project

Prenatal influences on the development of offspring asthma

Our group is specialized in reproductive immunology and allergy; we study how influences during pregnancy such as prenatal exposure to antibiotics, maternal asthma or non-pathogenic bacteria, affect fetal and neonatal development as well as disease susceptibility in early life. For more information about our current projects, please see www.conradlab.net

Lab Members

Fariz Kahhaleh
Fariz Kahhaleh
PhD student

fariz.kahhaleh(at)charite.de

Jeanne Arntz
Jeanne Arntz
PhD student

jeanne.arntz(at)charite.de

Swarali Datye
Swarali Datye
PhD student

swarali.datye(at)charite.de 

Moumen Alhasan
Moumen Alhasan
PhD student

moumen.alhasan(at)charite.de

+49 30 450 524 232

Publications

Dürr Lab

Mucosal Immunity

Dr. Claudia Dürr
Dr. Claudia Dürr
PI Mucosal Immunity
 

 claudia.duerr(at)charite.de

+49 (0)30 450 524 364

Projects

Due to respiration, our lungs are in continuous contact with the surrounding environment, sampling several liters of air each minute. Despite this perpetual exposure to potential pathogens and antigens, the lungs are maintained in a quiescent, non-inflamed state. Pulmonary infection, exposure to allergens or contact with hazardous materials, however, can initiate an efficient immune response to eradicate the invading organism or particle. In the case of allergy, some individuals mount an excessive immune response, which can manifest as asthma or respiratory allergy and is to a large extent triggered by deregulated type 2 immunity and respective cytokines. T helper 2 cells and the recently identified population of group 2 innate lymphoid cells (ILC2s) are the main source of type 2 signature cytokines. Importantly, ILC2s are committed to type 2 immunity and thus able to elicit beneficial responses, but can also exhibit excessive type 2 immune activity if dysregulated. The Duerr laboratory studies the underlying mechanisms of ILC2 regulation and function during development and ontogeny with the focus on pulmonary immunity. With our work, we hope to expand the knowledge of basic research in lung immunity to facilitate the development and identification of novel therapeutic strategies to improve lung health and thereby overall life quality.

 

Lab Members

Sofia Helfrich
Sofia Helfrich
PhD student

sofia.helfrich(at)charite.de

+49 30 450 524 047

Publications

Klose Lab

Neuro-immune Interactions

Dr. Christoph Klose
Dr. Christoph Klose
PI Neuro-immune Interactions

christoph.klose(at)charite.de

+49 (0)30 450 524 364

Projects

The nervous system and the immune system are the two large sensory units of the body, which perpetually monitor tissue integrity and mount effector responses upon disturbance of tissue hemostasis. However, how these two sensory systems exchange information and coordinate tissue protective responses remains elusive. Our research has recently exposed signaling pathways, by which the nervous system regulates innate lymphoid cells (ILCs) and type 2 immune responses via the production of neuropeptides (neuromedin U) and neurotransmitters (norepinephrine). ILCs are an emerging population of tissue-resident innate immune cells enriched at mucosal barriers, which can mount either protective or detrimental immune response at barrier surfaces. While we begin to understand some of the tissue-specific cues, which regulate immune activation at barrier surfaces, neuronal regulation of immune responses is still almost a black box. In order to systematically investigate neuro-immune crosstalk at mucosal surfaces in health and disease, we have developed elegant genetic tools, which allow experimental manipulation of neurons and ILCs. Taken together, combing cutting-edge technologies in the fields of immunology, neuroscience and genomics, will enable us to conceptually understand neuro-immune interaction and uncover signaling pathways that have the potential to be therapeutically harnessed.

Lab Members

Karoline Troch
Karoline Troch
MD student

karoline.troch(at)charite.de

Xuemei Gao
Xuemei Gao
PhD student

xuemei.gao(at)charite.de

Dr. Pierre Leclère
Dr. Pierre Leclère
Postdoc

pierre.leclere(at)charite.de

Alexandra Preußer
Alexandra Preußer
Master student

alexandra.preusser(at)charite.de

Sotiria Boulekou
Sotiria Boulekou
PhD student

sotiria.boulekou(at)charite.de

Dr. Katja Julika Jarick
Dr. Katja Julika Jarick
Postdoc

katja.jarick(at)charite.de

Dr. Divija D. Deshpande
Dr. Divija D. Deshpande
Postdoc

divija.deshpande(at)charite.de

+49 30 450 524359

Patrycja Topczewska
Patrycja Topczewska
PhD student

+40 30 524 234

Dr. Manuel Jakob
Dr. Manuel Jakob
Postdoc

+49 30 450 524 357

Vladislava Stokic-Trtica
Vladislava Stokic-Trtica
PhD student

vladislava.stokic-trtica(at)charite.de

+49 (0)30 450 524 234

Publications

1. Gronke K., P.P. Hernandez, J. Zimmermann, C.S.N. Klose, M. Kofoed-Branzk, F. Guendel, M. Witkowski, C. Tizian, L. Amann, F. Schumacher, H. Glatt, A. Triantafyllopoulou, A. Diefenbach
Nature, 566:249-253
2019
2. C.S.N. Klose, D. Artis
Current opinion in immunology, 56:94-99
2018
3. C. Chu, S. Moriyama, Z. Li, L. Zhou, A.L. Flamar, C.S.N. Klose, J.B. Moeller, G.G. Putzel, D.R. Withers, G.F. Sonnenberg, D. Artis
Cell reports, 23, 3750-3758
2018

Hamann Lab

Mucosal Immunity

Dr. Lutz Hamann
Dr. Lutz Hamann
PI Genetic variance within the innate immune system

lutz.hamann(at)charite.de

+49 (0)30 450 524 232

Project

Innate immune response and healthy aging

Aging is a multifactorial process resulting in accumulation of cellular damage, finally followed by the onset of aging-related diseases such as cardiovascular diseases, chronic lung diseases, cancer, and several more. One characteristic trait of the elderly is a chronically low level of inflammation, called inflamm-aging, that has been associated with the onset of aging-related diseases. Genetic variations that alter the innate immune response are not only associated with combating infectious diseases but also influence the onset of aging-related diseases. Our hypothesis is that genetic variations that impair innate immune response may be positively associated with healthy aging, thereby providing an example for antagonistic pleiotropy.

Lab Members

Christoph Kleinle
Christoph Kleinle
PhD student

Publications