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

Publications

Lenz M, Eichler A, Kruse P, Strehl A, Rodriguez-Rozada S, Goren I, Yogev N, Frank S, Waisman A, Deller T, Jung S, Maggio N and Vlachos A: Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation. Front Immunol; doi: 10.3389/fimmu.2020.614509 (2020).

Boeck M, Thien A, Wolf J, Hagemeyer N, Laich Y, Yusuf D, Backofen R, Zhang P, Boneva S, Stahl A, Hilgendorf I, Agostini H, Prinz M, Wieghofer P, Schlunck G, Schlecht A, Lange C: Temporospatial distribution and transcriptional profile of retinal microglia in the oxygen-induced retinopathy mouse model. Glia, 68(9):1859-1873 (2020).

Mossad O, Erny D: The microbiota-microglia axis in CNS disorders. Brain Pathol; doi: 10.1111/bpa.12908 (2020).

Erny D, Jakobsdóttir KB, Prinz M: Neuropathological evaluation of vertebrate brain aged ~ 245 years. Acta Neuropathol; doi: 10.1007/s00401-020-02237-4 (2020).

Fernández-Zapata C, Leman JKH, Priller J, Böttcher C: The use and limitations of single-cell mass cytometry for studying human microglia function. Brain Pathol; doi: 10.1111/bpa.12909 (2020).

Rolfes S, Munro DAD, Lyras EM, Matute E, Ouk K, Harms C, Böttcher C, Priller J: Lentiviral delivery of human erythropoietin attenuates hippocampal atrophy and improves cognition in the R6/2 mouse model of Huntington’s disease. Neurobiol Dis. 144:105024; doi: 10.1016/j.nbd.2020.105024 (2020).

Oschwald A, Petry P, Kierdorf K and Erny D: CNS Macrophages and Infant Infections. Front. Immunol., doi: 10.3389/fimmu.2020.02123 (2020).

Boneva SK, Wolf J, Rosmus DD, Schlecht A, Prinz G, Laich Y, Boeck M, Zhang P, Hilgendorf I, Stahl A, Reinhard T, Bainbridge J, Schlunck G, Agostini H, Wieghofer P and Lange CAK: Transcriptional Profiling Uncovers Human Hyalocytes as a Unique Innate Immune Cell Population. Front Immunol, doi.org/10.3389/fimmu.2020.567274 (2020).

Böttcher C*, Fernández-Zapata C*, Snijders GJL, Schlickeiser S, Sneeboer MAM, Kunkel D, De Witte LD*, Priller J*: Single-cell mass cytometry of microglia in major depressive disorder reveals a non-inflammatory phenotype with increased homeostatic marker expression. Transl Psychiatry 10(1), 310; doi: 10.1038/s41398-020-00992-2 (2020).  *equal contribution

Bassett DS, Cullen KE, Eickhoff SB, Farah MJ, Goda Y, Haggard P, Hu H, Hurd YL, Josselyn SA, Khakh BS, Knoblich JA, Poirazi P, Poldrack RA, Prinz M, Roelfsema PR, Spires-Jones TL, Sur M, Ueda HR: Reflections on the past two decades of neuroscience. Nat Rev Neuroci 21(10), 524-534 (2020).

Böttcher C*, van der Poel M*, Fernández-Zapata C*, Schlickeiser S, Leman JKH, Hsiao CC, Mizee MR, Adelia, Vincenten MCJ, Kunkel D, Huitinga I*, Hamann J*, Priller J*: Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis. Acta Neuropathol Commun 8, 136; doi: 10.1186/s40478-020-01010-8 (2020). *equal contribution

Ormel PR, Böttcher C, Gigase FAJ, Missall RD, van Zuiden W, Fernández Zapata MC, Ilhan D, de Goeij M, Udine E, Sommer IEC, Priller J, Raj T, Kahn RS, Hol EM, de Witte LD: A characterization of the molecular phenotype and inflammatory response of schizophrenia patient-derived microglia.like cells. Brain Behav Immun. S0889-1591(19)31489-8; doi: 10.1016/j.bbi.2020.08.012 (2020).

Mezö C, Dokalis N, Mossad O, Staszewski O, Neuber J, Yilmaz B, Schnepf D, Gomez de Agüero M, Ganal-Vonarbung SC, Macpherson AJ, Meyer-Luehmann M, Staeheli P, Blank T, Prinz M, Erny D: Different effects of constitutive and induced microbiota modulation on microglia in a mouse model of Alzheimers’s disease. Acta Neuropathologia Communications 8, 119 (2020).

Masuda T, Amann L, Sankowski R, Staszewski O, Lenz M, d´Errico P, Snaidero N, Jordão MJC, Böttcher C, Kierdorf K, Jung S, Priller J, Misgeld T, Vlachos A, Meyer Luehmann M, Knobeloch KP and Prinz M: Novel Hexb-based tools for studying microglia in the CNS. Nature Immunology 21, 802–815 (2020).

Baasch S, Ruzsics Z and Henneke P: Cytomegaloviruses and Macrophages—Friends and Foes From Early on? Front Immunol 11 (793), doi: 10.3389/fimmu.2020.00793 (2020).

Drost N, Houtman J, Cseresnyés Z, Niesner R, Rinnenthal JL, Miller KR, Prokop S and Heppner FL: Scientific Reports volume 10, Article number: 7152 (2020) The Amyloid-beta rich CNS environment alters myeloid cell functionality independent of their origin. Sci Rep 10: 7152, doi: 10.1038/s41598-020-63989-3 (2020).

Schlecht A, Boneva S, Gruber M, Zhang P, Horres R, Bucher F, Auw-Haedrich C, Hansen L, Stahl A, Hilgendorf I, Agostini H, Wieghofer P, Schlunck G, Wolf J, Lange CAK: Transcriptomic Characterization of Human Choroidal Neovascular Membranes Identifies Calprotectin as a Novel Biomarker for Patients With Age-Related Macular Degeneration. Am J Pathol S0002-9440(20)30201-7, doi: 10.1016/j.ajpath.2020.04.004 (2020).

Amann L, Prinz M: The origin, fate and function of macrophages in the peripheral nervous system – an update. In Immunol  32(11), 709-717 (2020).

Ydens E, Amann L, Asselbergh B, Scott CL, Martens L, Sichien D, Mossad O, Blank T, De Prijck D, Low D, Masuda T, Saeys Y, Timmerman V, Stumm R, Ginhoux F, Prinz M, Janssens S and Guilliams M: Profiling peripheral nerve macrophages reveals two macrophage subsets with distinct localization, transcriptome and response to injury. Nature Neuroscience 23, 676–689 (2020).

Dembny P, Newman AG, Singh M, Hinz M, Szczepek M, Krüger C, Adalbert R, Dzaye O,Trimbuch T, Wallach T, Kleinau G, Derkow K, Richard BC, Schipke C, Scheidereit C, Stachelscheid H, Golenbock D, Peters O, Coleman M, Heppner FL, Scheerer P, Tarabykin V, Ruprecht K, Izsvák Z, Mayer J, and Lehnardt S: Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors. JCI Insight 5(7): e131093, doi: 10.1172/jci.insight.131093 (2020).

Hamarsheh S, Osswald L, Saller BS, Unger S, De Feo D, Vinnakota JM, Konantz M, Uhl FM, Becker H, Lübbert M, Shoumariyeh K, Schürch C, Andrieux G, Venhoff N, Schmitt-Graeff A, Duquesne S, Pfeifer D, Cooper MA, Lengerke C, Boerries M, Duyster J, Niemeyer CM, Erlacher M, Blazar BR, Becher B, Groß O, Brummer T and Zeiser R: Oncogenic KrasG12D causes myeloproliferation via NLRP3 inflammasome activation. Nature Communications 11, 1659 (2020).

Duscha A, Gisevius B, Hirschberg S, Yissachar N, Stangl GI, Eilers E, Bader V, Haase S, Kaisler J, David C, Schneider R, Troisi R, Zent D, Hegelmaier T, Dokalis N, Gerstein S, Del Mare-Roumani S, Amidror S, Staszewski O, Poschmann G, Stühler K, Hirche F, Balogh A, Kempa S, Träger P, Zaiss MM, Holm JB, Massa MG, Nielsen HB, Faissner A, Lukas C, Gatermann SG, Scholz M, Przuntek H, Prinz M, Forslund SK, Winklhofer KF, Müller DN, Linker RA, Gold R, Haghikia A: Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism. Cell,  180(6),1067-1080.e16 8 (2020).

Erny D, Prinz M: How microbiota shape microglial phenotypes and epigenetics. Glia 68(8), 1655-1672. doi: 10.1002/glia.23822 (2020).

Hotter B, Hoffmann S, Ulm L, Montaner J, Bustamante A, Meisel C, Meisel A: Inflammatory and stress markers predicting pneumonia, outcome, and etiology in patients with stroke. Biomarkers for predicting pneumonia, functional outcome, and death after stroke. Neurol Neuroimmunol Neuroinflamm 7(3): e692, doi: 10.1212/NXI.0000000000000692 (2020).

Kierdorf K, Hersperger F, Sharrock J, Vincent CM, Ustaoglu P, Dou J, Gyoergy A, Groß O, Siekhaus DE, Dionne MS: Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. Elife 9. pii: e51595 (2020).

Wallach T, Wetzel M, Dembny P, Staszewski O, Krüger C, Buonfiglioli A, Prinz M, Lehnardt S: Identification of CNS injury-related microRNAs as novel Toll-like Receptor 7/8 signaling ctivators by Small RNA Sequencing. Cells 9(1), pii: E186 (2020).

Kolter J, Kierdorf K, Henneke P: Origin and Differentiation of Nerve-Associated Macrophages. J Immunol 204, 271-289; doi: 10.4049/jimmunol.org/content/204/2/271 (2020).

Bell OH, Copland DA, AWard A, Nicholson LB, Lange CAK,Chu CJ and Dick AD: Single Eye mRNA-Seq Reveals Normalisation of the Retinal Microglial Transcriptome Following Acute Inflammation. Front Immunol 10 (3033), doi: 10.3389/fimmu.2019.03033 (2020).

Böttcher C, Fernández-Zapata C, Schlickeiser S, Kunkel D, Schulz AR, Mei HE, Weidinger C, Gieß RM, Asseyer S, Siegmund B, Paul F, Ruprecht K, Priller J: Multi-parameter immune profiling of peripheral blood mononuclear cells by multiplexed single-cell mass cytometry in patients with early multiple sclerosis. Sci Rep 9(1), 19471. doi: 10.1038/s41598-019-55852-x 8 (2019).

Sankowski R, Strohl JJ, Huerta TS, Nasiri E, Mazzarello AN, D’Abramo C, Cheng KF, Staszewski O, Prinz M, Huerta PT, and Al-Abed Y: Endogenous retroviruses are associated with hippocampus-based memory impairment. PNAS 116 (51) 25982-25990; doi.org/10.1073/pnas.182216411 (2019).

R Mathew N, Vinnakota JM, Apostolova P, Erny D, Hamarsheh S, Andrieux G, Kim JS, Hanke K, Goldmann T, Chappell-Maor L, El-Khawanky N, Ihorst G, Schmidt D, Duyster J, Finke J, Blank T, Boerries M, Blazar BR, Jung S, Prinz M, Zeiser R: Graft-versus-host disease of the CNS is mediated by TNF upregulation in microglia. J Clin Invest, pii: 130272; doi: 10.1172/JCI130272 (2019).

Geirsdottir L, David E, Keren-Shaul H, Weiner A, Bohlen SC,  Neuber J, Balic A, Giladi A, Sheban F, Dutertre CA, Pfeifle C, Peri F, Raffo-Romero A, Vizioli J, Matiasek K, Scheiwe C, Meckel S, Mätz-Rensing K, van der Meer F, Thormodsson FR, Stadelmann C, Zilkha N, Kimchi T, Ginhoux F, Ulitsky I, Erny D, Amit I, Prinz M: Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program. Cell 179 (7), 1609-1622.e16; doi: 10.1016/j.cell.2019.11.010 (2019).

Ziegler JF, Böttcher C, Letizia M, Yerinde C, Wu H, Freise I, Rodriguez-Sillke Y, Stoyanova AK, Kreis ME, Asbach P, Kunkel D, Priller J, Anagnostopoulos I, Kühl AA, Miehle K, Stumvoll M, Tran F, Fredrich B, Forster M, Franke A, Bojarski C, Glauben R, Löscher BS, Siegmund B, Weidinger C: Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn’s disease. Nat Commun 10, 5629; doi.org/10.1038/s41467-019-13559-7 (2019).