The goal of the NeuroMac initiative

The goal of the NeuroMac initiative is to obtain insights into the diverse functions of myeloid cells in the CNS during development, health and disease. A particular focus will be on parenchymal macrophages (microglia), circulating monocytes and bone marrow myeloid cells (e.g. myeloid progenitors). Combining studies of brain myeloid cell development and homeostasis, neurobiology, cell migration and neuropathology in one research initiative will enable a fruitful and productive interaction between the groups involved.

Research Program

Publications

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).

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).

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).

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).

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).