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The goal of NeuroMac

The main goal of the second funding period is to better understand the molecular mechanisms of myeloid cell diversity in the CNS and the interactions of microglia with neurons and other glial cells during development, health and perturbation. In detail, we want to:

  • explore the molecular mechanisms determining myeloid cell identity in the healthy and diseased CNS (Area A)
  • examine the spatial distribution of brain myeloid cells (Area A)
  • identify the cellular mechanisms for the establishment context-associated microglia states and for the interactions of myeloid cells with other cells in the affected CNS (Areas A, B)
  • use myeloid cells therapeutically in preclinical models of CNS diseases (Area B)
Research Program

News

Publications

Giesler S, Riemer R, Lowinus T, Zeiser R: Immune-mediated colitis after immune checkpoint inhibitor therapy . Trends Mol Med S1471-4914(24)00266-1; doi: 10.1016/j.molmed.2024.09.009 (2024).

Nath S, Martínez Santamaría JC, Chu Y-H, Choi JS, Conforti P, Lin J-D, Sankowski R, Amann L, Galanis C, Wu K, Deshpande SS, Vlachos A, Prinz M, Lee JK, Schachtrup C: Interaction between subventricular zone microglia and neural stem cells impacts the neurogenic response in a mouse model of cortical ischemic stroke. Nat Commun 15:9095. doi: 10.1038/s41467-024-53217-1 (2024).

Bøstrand SMK, Seeker LA, Bestard-Cuche N, Kazakou N-L, Jäkel S, Kenkhuis B,
Henderson NC, de Bot ST, van Roon-Mom WMC, Priller J and Williams A: Mapping the glial transcriptome in Huntington’s disease using snRNAseq: selective disruption of glial signatures across brain regions. Acta Neuropathol Commun 12:165; doi: 10.1186/s40478-024-01871-3 (2024).

Dumas AA, Gasull AD, Prinz M: Beyond borders: the choroid plexus-immune communication during neuroinflammation. Signal Transduct Target Ther 9:278. doi: 10.1038/s41392-024-01997-9 (2024).

Hasavci D, Blank T: A microglial compliment: controlling neuronal function from within. Signal Transduct Target Ther 9(1):267; doi: 10.1038/s41392-024-01989-9 (2024).

Schmidt D, Endres C, Hoefflin R, Andrieux G, Zwick M, Karantzelis N, Staehle HF, Vinnakota JM, Duquesne S, Mozaffari Jovein M, Pfeifer D, Becker H, Blazar BR, Zähringer A, Duyster J, Brummer T, Boerries M, Baumeister J, Shoumariyeh K, Li J, Green AR, Heidel FH, Tirosh I, Pahl HL, Leimkühler N, Köhler N, de Toledo MAS, Koschmieder S, Zeiser R: Oncogenic Calreticulin Induces Immune Escape by Stimulating TGF-β Expression and Regulatory T Cell Expansion in the Bone Marrow Microenvironment. Cancer Res 84(18):2985-3003; doi: 10.1158/0008-5472.CAN-23-3553 (2024).

Früholz I, Meyer-Luehmann M: The intricate interplay between microglia and adult neurogenesis in Alzheimer’s disease . Front Cell Neurosci 18:1456253; doi: 10.3389/fncel.2024.1456253 (2024).

Lisowski P, Lickfett S, Rybak-Wolf A, Menacho C, Le S, Pentimalli TM, Notopoulou S, Dykstra W, Oehler D, López-Calcerrada S, Mlody B, Otto M, Wu M, Richter Y, Roth P, Anand R, Kulka LAM, Meierhofer D, Glazar P, Legnini I, Telugu NS, Hahn T, Neuendorf N, Miller DC, Böddrich A, Polzin A, Mayatepek E, Diecke S, Olzscha H, Kirstein J, Ugalde C, Petrakis S, Cambridge S, Rajewsky N, Kühn R, Wanker EE, Priller J, Metzger JJ & Prigione A: Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure. Nat Commun 15:7027. doi: 10.1038/s41467-024-51216-w (2024).

Wogram E, Sümpelmann F, Dong W, Rawat E, Fernández Maestre I, Fu D, Braswell B, Khalil A, Buescher JM, Mittler G, Borner GHH, Vlachos A, Tholen S, Schilling O, Bell GW, Rambold AS, Akhtar A, Schnell O, Beck J, Abu-Remaileh M, Prinz M, Jaenisch R: Rapid phagosome isolation enables unbiased multiomic analysis of human microglial phagosomes. Immunity; doi:https://doi.org/10.1016/j.immuni.2024.07.019 (2024).

Biniaris-Georgallis S-I, Aschman T, Stergioula K, Schreiber F, Jafari V, Taranko A, Karmalkar T, Kasapi A, Rovis TL, Jelencic V, Bejarano DA, Fabry L, Papacharalampous M, Mattiola I, Molgora M, Hou J, Hublitz KW, Heinrich F, Guerra GM, Durek P, Patone G, Lindberg EL, Maatz H, Hölsken O, … Triantafyllopoulou A: Amplification of autoimmune organ damage by NKp46-activated ILC1s. Nature 634(8035):952-960; doi: 10.1038/s41586-024-07907-x (2024).

Topczewska PM, Savvopoulou A, Cosovanu C, Klose CSN: Transcriptional profiling identifies IL-33-expressing intestinal stromal cells as a signaling hub poised to interact with enteric neurons.
Front Cell Dev Biol 12:1420313; doi: 10.3389/fcell.2024.1420313 (2024).

Wenger V, Zeiser R: Deciphering the role of the major histocompatibility complex, the intestinal microbiome and metabolites in the pathogenesis of acute graft-versus-host disease. Best Pract Res Clin Haematol 37(3):101567; doi: 10.1016/j.beha.2024.101567 (2024).

Zimmermann JA, Lucht K, Stecher M, Badhan C, Glaser KM, Epple MW, Koch LR, Deboutte W, Manke T, Ebnet K, Brinkmann F, Fehler O, Vogl T, Schuster E-M, Bremser A, Buescher JM, Rambold AS: Functional multi-organelle units control inflammatory lipid metabolism of macrophages. Nat Cell Biol 26(8):1261-1273; doi: 10.1038/s41556-024-01457-0 (2024).

Rosmus D-D, Koch J, Hausmann A, Chiot A, Arnhold F, Masuda T, Kierdorf K, Marie S, Kuhrt H, Fröba J, Wolf J,
Boneva S, Gericke M, Ajami B, Prinz M, Lange C and Wieghofer P: Redefining the ontogeny of hyalocytes as yolk sac‑derived tissue‑resident macrophages of the vitreous body. J Neuroinflammation 21:168; doi: 10.1186/s12974-024-03110-x (2024).

Moeed A, Thilmany N, Beck F, Puthussery BK, Ortmann N, Haimovici A, Badr MT, Haghighi EB, Boerries M, Öllinger R, Rad R, Kirschnek S, Gentle IE, Donakonda S, Petric PP, Hummel JF, Pfaffendorf E, Zanetta P, Schell C Schwemmle M, Weber A, Häcker G: The Caspase-Activated DNase drives inflammation and contributes to defense against viral infection. Cell Death Differ 31(7):924-937; doi: 10.1038/s41418-024-01320-7 (2024).

Colcerasa A, Friedrich F, Melesina J, Moser P, Vogelmann A, Tzortzoglou P, Neuwirt E, Sum M, Robaa D, Zhang L, Ramos-Morales E, Romier C, Einsle O, Metzger E, Schüle R, Groß O, Sippl W, Jung M: Structure-Activity Studies of 1,2,4-Oxadiazoles for the Inhibition of the NAD+-Dependent Lysine Deacylase Sirtuin 2. J Med Chem 67(12):10076-10095; doi: 10.1021/acs.jmedchem.4c00229 (2024).

Talvard-Balland N, Braun LM, Dixon KO, Zwick M, Engel H, Hartmann A, Duquesne S, Penter L, Andrieux G, Rindlisbacher L, Acerbis A, Ehmann J, Köllerer C, Ansuinelli M, Rettig A, Moschallski K, Apostolova P, Brummer T, Illert AL, Schramm MA, Cheng Y, Köttgen A, Duyster Y, Menssen HD, Ritz J, Blazar BR, Boerries M, Schmitt-Gräff A, Sariipek N, Van Galen N, Buescher JM, Cabezas-Wallscheid N, Pahl HL, Pearce EL, Soiffer EJ, Wu CJ, Vago L, Becher B, Köhler N, Wertheimer T,Kuchroo VK, and Zeiser R: Oncogene-induced TIM-3 ligand expression dictates susceptibility to anti–TIM-3 therapy in mice. J Clin Invest 134(16):e177460; doi: 10.1172/JCI177460 (2024).

Petry P, Aktories P, Oschwald A, Kierdorf K: Protocol for long-term monocultures of murine macrophages derived from distinct adult tissues. STAR Protoc 5(3):103145; doi: 10.1016/j.xpro.2024.103145 (2024).

Munro DAD, Bestard-Cuche N, McQuaid C, Chagnot A, Shabestari SK, Chadarevian JP, Maheshwari U, Szymkowiak S, Morris K, Mohammad M, Corsinotti A, Bradford B, Mabbott N, Lennen RJ, Jansen MA, Pridans C, McColl BW, Keller A, Blurton-Jones M, Montagne A, Williams A, Priller J: Microglia protect against age-associated brain pathologies. Neuron S0896-6273(24)00365-9; doi: 10.1016/j.neuron.2024.05.018 (2024).

Vinnakota JM, Adams RC, Athanassopoulos D, Schmidt D, Biavasco F, Zähringer A, Erny D, Schwabenland M, Langenbach M, Wenger V, Salié H, Cook J, Mossad O, Andrieux G, Dersch R, Rauer S, Duquesne S, Monaco G, Wolf P, Blank T, Häne P, Greter M, Becher B, Henneke P, Pfeifer D, Blazar BR, Duyster J, Boerries M, Köhler N, Chhatbar CM, Bengsch B, PrinzM, Zeiser R: Anti-PD-1 cancer immunotherapy induces central nervous system immune-related adverse events by microglia activation. Sci Transl Med 16(751):eadj9672; doi: 10.1126/scitranslmed.adj9672 (2024).

Trzebanski S, Kim JS, Larossi N, Raanan A, Kancheva D, Bastos J, Haddad M, Solomon A, Sivan E, Aizik D, Sekeresova Kralova J, Gross-Vered M, Boura-Halfon S, Lapidot T, Alon R, Movahedi K, Jung S: Classical monocyte ontogeny dictates their functions and fates as tissue macrophages. Immunity 57(6):1225-1242.e6; doi: 10.1016/j.immuni.2024.04.019 (2024).

Kessler S, Burke B, Andrieux G, Schinköthe J, Hamberger L, Kacza J,Zhan S, Reasoner C, Dutt TS, Kaukab Osman M, Henao-Tamayo M, Staniek J, Villena Ossa JF, Frank DT, Ma W, Ulrich R, Cathomen T, Boerries M, Rizzi M, Beer M, Schwemmle M, Reuther P, Schountz T, and Ciminski K: Deciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level. Nat Commun 15(1):4500; doi: 10.1038/s41467-024-48934-6 (2024).

Bredow C, Thery F, Wirth EK, Ochs S, Kespohl M, Kleinau G, Kelm N, Gimber N, Schmoranzer J, Voss M, Klingel K, Spranger J, Renko K, Ralser M, Mülleder M, Heuser A, Knobeloch KP, Scheerer P, Kirwan J, Brüning U, Berndt N, Impens F, Beling A: ISG15 blocks cardiac glycolysis and ensures sufficient mitochondrial energy production during Coxsackievirus B3 infection . Cardiovasc Res 120(6):644-657; doi: 10.1093/cvr/cvae026 (2024).

Röwekamp I, Maschirow L, Rabes A, Fiocca Vernengo F, Hamann L, Heinz GA, Mashreghi MF, Caesar S, Milek M, Fagundes Fonseca AC, Wienhold SM, Nouailles G, Yao L, Mousavi S, Bruder D, Boehme JD, Puzianowska-Kuznicka M, Beule D, Witzenrath M; CAPNETZ Study Group; Löhning M, Klose CSN, Heimesaat MM, Diefenbach A, Opitz B: IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota. Proc Natl Acad Sci U S A 121(22):e2310864121; doi: 10.1073/pnas.2310864121 (2024).

Surala M, Soso-Zdravkovic L, Munro D, Rifat A, Ouk K, Vida I, Priller J, Madry C: Lifelong absence of microglia alters hippocampal glutamatergic networks but not synapse and spine density. EMBO Rep 25(5):2348-2374; doi: 10.1038/s44319-024-00130-9 (2024).

Sekeresova Kralova J, Fidel L, Donic C, Ben-Dor S, Jung S: Draft genome of Kazachstania heterogenica var. weizmannii, a commensal fungus of the mouse digestive tract. Microbiol Resour Announc 13(4):e0011524; doi: 10.1128/mra.00115-24 (2024).

Barboy O, Bercovich A, Li H, Eyal-Lubling Y, Yalin A, Shapir Itai Y, Abadie K, Zada M, David E, Shlomi-Loubaton S, Katzenelenbogen Y, Adhemar Jaitin D, Gur C, Yofe I, Feferman T, Cohen M, Dahan R, Newell EW, Lifshitz A, Tanay A & Amit I: Modeling T cell temporal response to cancer immunotherapy rationalizes development of combinatorial treatment protocols. Nat Cancer 5(5):742-759; doi: 10.1038/s43018-024-00734-z (2024).

McGurran H, Kumbol V, Krüger C, Wallach T, Lehnardt S: miR-154-5p Is a Novel Endogenous Ligand for TLR7 Inducing Microglial Activation and Neuronal Injury. Cells 13(5):407; doi: 10.3390/cells13050407 (2014).

Virtuoso A, Galanis C, Lenz M, Papa M, Vlachos A: Regional Microglial Response in Entorhino-Hippocampal Slice Cultures to Schaffer Collateral Lesion and Metalloproteinases Modulation. Int J Mol Sci 25(4):2346; doi: 10.3390/ijms25042346 (2024).

Dalmau Gasull A, Glavan M, Reddy Samawar SK, Kapupara K, Kelk J, Rubio M, Fumagalli S, Sorokin L, Vivien D, Prinz M: The niche matters: origin, function and fate of CNS-associated macrophages during health and disease. Acta Neuropathol 147(1): 37 (2024).

Weinelt N, Wächtershäuser KN, Celik G, Jeiler B, Gollin I, Zein L, Smith S, Andrieux G, Das T, Roedig J, Feist L, Rotter B, Boerries M, Pampaloni F, van Wijk SJL: LUBAC-mediated M1 Ub regulates necroptosis by segregating the cellular distribution of active MLKL. Cell Death Dis 15(1):77; doi: 10.1038/s41419-024-06447-6 (2024).

Hersperger F, Meyring T, Weber P, Chhatbar C, Monaco G, Dionne MS, Paeschke K, Prinz M, Groß O, Classen AK, Kierdorf K: DNA damage signaling in Drosophila macrophages modulates systemic cytokine levels in response to oxidative stress. Elife 12:RP86700; doi: 10.7554/eLife.86700 (2024).

Kruse P, Brandes G, Hemeling H, Huang Z, Wrede C, Hegermann J, Vlachos A, Lenz M: Synaptopodin Regulates Denervation-Induced Plasticity at Hippocampal Mossy Fiber Synapses. Cells 13(2):114; doi: 10.3390/cells13020114 (2024).

Torella L, Klermund J, Bilbao-Arribas M, Tamayo I, Andrieux G, Chmielewski KO, Vales A, Olagüe C, Moreno-Luqui D, Raimondi I, Abad A, Torrens-Baile J, Salido E, Huarte M, Hernaez M, Boerries M, Cathomen T, Zabaleta N, Gonzalez-Aseguinolaza G: Efficient and safe therapeutic use of paired Cas9-nickases for primary hyperoxaluria type 1. EMBO Mol Med 16(1):112-131; doi: 10.1038/s44321-023-00008-8 (2024).

Kirschenbaum, D, Xie, K, Ingelfinger, F, Katzenelenbogen, Y, Abadie, K, Look, T, Sheban, F, Phan, TS, Li, B, Zwicky, P, Yofe, I, David, E, Mazuz, K, Hou, J, Chen, Y, Shaim, H, Shanley, M, Becker, S, Qian, J, Colonna, M, Ginhoux, F, Rezvani, K, Theis, FJ, Yosef, N, Weiss, T, Weiner, A, & Amit, I Time-resolved single-cell transcriptomics defines immune trajectories in glioblastoma. Cell, 187(1):149-165.e23. https://doi: 10.1016/j.cell.2023.11.032 (2024).

Sankowski R, Süß P, Benkendorff A, Böttcher C, Fernandez-Zapata C, Chhatbar C, Cahueau J, Monaco G, Dalmau Gasull A, Khavaran A, Grauvogel J, Scheiwe C, Shah MJ, Heiland DH, Schnell O, Markfeld-Erol F, Kunze M, Zeiser R, Priller J, Prinz M: Multiomic spatial landscape of innate immune cells at human central nervous system borders. Nat Med 30(1):186-198; doi: 10.1038/s41591-023-02673-1 (2024).

Vinnakota, JM, Biavasco, F, Schwabenland, M, Chatbar, C, Adams, RC, Erny, D, Duquesne, S, El Khawanky, N, Schmidt, D, Fetsch, V, Zähringer, A, Salié, H, Athanassopoulos, D, Braun, LM, Javorniczky, RN, Ho, JNHG, Kierdorf, K, Marks, R, Wäsch, R, Simonetta, F, Andrieux, G, Pfeifer, D, Monaco, G, Capitini, C, Fry, TJ, Blank, T, Blazar, BR, Wagner, E, Theobald, M, Sommer, C, Stelljes, M, Reicherts, C, Jeibmann, A, Schittenhelm, J, Monoranu, JM, Rosenwald, A, Kortüm, M, Rasche, L, Einsele, H, Philipp, T, Meyer, PT, Brumberg, J, Völkl, S, Mackensen, A, Coras, R, von Bergwelt-Baildon, M, Albert, NL, Bartos, LM, Brendel, M, Holzgreve, A, Boerries, M, Mackall, CL, Duyster, J, Henneke, P, Priller, J, Köhler, N, Strübing, F, Bengsch, B, Ruella, M, Subklewe, M, von Baumgarten, L, Gill, S, Prinz, M*, & Zeiser, R* Targeting TGF-β-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity-syndrome (ICANS). Nat Cancer, in press (2024).

Hersperger F, Kastl M, Paeschke K, Kierdorf K: Hemocyte Nuclei Isolation from Adult Drosophila melanogaster for snRNA-seq. Methods Mol Biol 2713:71-79; doi: 10.1007/978-1-0716-3437-0_4 (2024).

Kastl M, Hersperger F, Kierdorf K, Paeschke K: Detection of G-Quadruplex DNA Structures in Macrophages. Methods Mol Biol 2713:453-462; doi: 10.1007/978-1-0716-3437-0_30 (2024).

Baasch S, Henschel J, Henneke P: Combined Host-Pathogen Fate Mapping to Investigate Lung Macrophages in Viral Infection. Methods Mol Biol 2713:347-361; doi: 10.1007/978-1-0716-3437-0_24 (2024).

Wu Y, Zehnle PMA, Rajak J, Koleci N, Andrieux G, Gallego-Villar L, Aumann K, Boerries M, Niemeyer CM, Flotho C, Bohler S, Erlacher M: BH3 mimetics and azacitidine show synergistic effects on juvenile myelomonocytic leukemia. Leukemia 38(1):136-148; doi: 10.1038/s41375-023-02079-5 (2024).

Voss M, Pinkert S, Kespohl M, Gimber N, Klingel K, Schmoranzer J, Laue M, Gaida M, Kloetzel P-M, Beling A: A Conserved Cysteine Residue in Coxsackievirus B3 Protein 3A with Implication for Elevated Virulence. Viruses 14(4), 769, doi: 10.3390/v14040769 (2022).