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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

Publications

Pinkert S, Kespohl M, Kelm N, Kaya Z, Heuser A, Klingel A, Beling A: Exploration of Analgesia with Tramadol in the Coxsackievirus B3 Myocarditis Mouse Model. Viruses 13(7):1222; doi: 10.3390/v13071222 (2021).

Kienle K, Glaser KM, Eickhoff S, Mihlan M, Knöpper K, Reátegui E, Epple MW, Gunzer M, Baumeister R, Tarrant TK, Germain RN, Irimia D, Kastenmüller W, Lämmermann T: Neutrophils self-limit swarming to contain bacterial growth in vivo. Science 372(6548):eabe7729; doi: 10.1126/science.abe7729 (2021).

Galanis C, Fellenz M, Becker D, Bold C, Lichtenthaler SF, Müller UC, Deller T and Vlachos A: Amyloid-Beta Mediates Homeostatic Synaptic Plasticity. J Neurosci 41(24):5157-5172; doi: 10.1523/JNEUROSCI.1820-20.2021 (2021).

Baasch S, Giansanti P, Kolter J, Riedl A, Forde AJ, Runge S, Zenke S, Elling R, Halenius A, Brabletz S, Hengel H, Kuster B, Brabletz T, Cicin-Sain L, Arens R, Vlachos A, Rohr JC, Stemmler MP, Kopf M, Ruzsics Z, Henneke P: Cytomegalovirus subverts macrophage identity. Cell 184, 1-20 (2021).

Schwabenland M, Salié H, Tanevski J, Killmer S, Salvat Lago M, Schlaak AE, Mayer L, Matschke J, Püschel K, Fitzek A, Ondruschka B, Mei HE, Boettler T, Neumann-Haefelin C, Hofmann M, Breithaupt A, Genc N, Stadelmann C, Saez-Rodriguez J, Bronsert P, Knobeloch K-P, Blank T, Thimme R, Glatzel M, Prinz M, Bengsch B: Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T cell interactions. Immunity; doi: https://doi.org/10.1016/j.immuni.2021.06.002 (2021).

Roncoroni M, Droesbeke B, Eguinoa I, De Ruyck K, D’Anna F, Yusuf D, Grüning B, Backofen R, Coppens F: A SARS-CoV-2 sequence submission tool for the European Nucleotide Archive. Bioinformatics;btab421; doi: 10.1093/bioinformatics/btab421 (2021).

Henneke P, Kierdorf K, Hall LJ, Sperandio M, Hornef M: Perinatal development of innate immune topology. Elife 10:e67793; doi: 10.7554/eLife.67793 (2021).

Friedrich M, Sankowski R, Bunse L, Kilian M, Green E, Ramallo Guevara C, Pusch S, Poschet G, Sanghvi K, Hahn M, Bunse T, Münch P, Gegner HM, Sonner JK, von Landenberg A, Cichon F, Aslan K, Trobisch T, Schirmer L, Abu-Sammour D, Kessler T, Ratliff M, Schrimpf D, Sahm F, Hopf C, Heiland DH, Schnell O, Beck J, Böttcher C, Fernandez-Zapata C, Priller J, Heiland S, Gutcher I, Quintana FJ, von Deimling A, Wick W, Prinz M & Platten M: Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas. Nature Cancer 2, 723–740 (2021).

Deczkowska A, David E, Ramadori P, Pfister D, Safran M, Baoguo At The, Giladi A, Jaitin DA, Barboy O, Cohen M, Yofe I, Gur C, Shlomi-Loubaton S, Henri S, Suhail Y, Qiu M, Kam S, Hermon H, Lahat E, Yakov GB, Cohen-Ezra O, Davidov Y, Likhter M, Goitein D, Roth S, Weber A, Malissen B, Weiner A, Ben-Ari Z, Heikenwälder M, Elinav W, Amit I: XCR1 + type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis. Nature Medicine 27, 1043–1054 (2021).

Klose CSN, Veiga-Fernandes H: Neuroimmune interactions in peripheral tissue. Eur J Immunol; doi: 10.1002/eji.202048812 (2021).

Clark IC, Gutiérrez-Vázquez C, Wheeler MA, Li Z, Rothhammer V, Linnerbauer M, Sanmarco LM, Guo L, Blain M, Zandee SEJ, Chao C-C, Batterman KV, Schwabenland M, Lotfy P, Tejeda-Velarde A, Hewson P, Manganeli Polonio C, Shultis MW, Salem Y, Tjon EC, Fonseca-Castro PH, Borucki DM, Alves de Lima K, Plasencia A, Abate AR, Rosene DL, Hodgetts KJ, Prinz M, Antel JP, Prat A, Quintana FJ: Barcoded viral tracing of single-cell interactions in central nervous system inflammation. Science 372(6540):eabf1230; doi: 10.1126/science.abf1230 (2021).

Jagdmann S, Berchtold D, Gutbier B, Witzenrath M, Meisel A, Meisel C, Dames C: Efficacy and safety of intratracheal IFN-γ treatment to reverse stroke-induced susceptibility to pulmonary bacterial infections. Journal of Neuroimmunology, DOI: 10.1016/j.jneuroim.2021.577568 (2021).

Hosp JA, Dressing A, Blazhenets G, Bormann T, Rau A, Schwabenland M, Thurow J, Wagner D, Waller C, Niesen WD, Frings L, Urbach H, Prinz M, Weiller C, Schroeter N, Meyer PT: Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain awab009; doi: 10.1093/brain/awab009 (2021).

Tavares‐Gomes L, Monney C, Neuhaus G, Francisco D, Solis D, Summerfield A, Erny D, Jagannathan V, Oevermann A: Transcriptome of microglia reveals a species‐specific expression profile in bovines with conserved and new signature genes. Glia; doi: 10.1002/glia.24002. Online ahead of print. (2021).

Lösslein AK, Lohrmann F, Scheuermann L, Gharun K, Neuber J, Kolter J, Forde AJ, Kleimeyer C, Poh YY, Mack M, Triantafyllopoulou A, Dunlap MD, Khader SA, Seidl M, Hölscher A, Hölscher C, Guan XL, Dorhoi A and Henneke P: Monocyte progenitors give rise to multinucleated giant cells. Nat Commun 12, 2027 (2021).

Moghadam ZM, Henneke P and Kolter J: From Flies to Men: ROS and the NADPH Oxidase in Phagocytes. Front Cell Dev Biol 9:628991; doi: 10.3389/fcell.2021.628991 (2021).

Pfister D, […] Amit I, […] Heikenwalder M: NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature 592, 450–456 (2021).

Emig RWiebke Knodt W, Krussig MJ, Zgierski-Johnston  CM, Gorka O, Groß O, Kohl P, Ravens U, Peyronnet R: Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing. Cells 10(3):663; doi: 10.3390/cells10030663 (2021).

Köhler N, Ruess DA, Kesselring R, Zeiser R: The Role of Immune Checkpoint Molecules for Relapse After Allogeneic Hematopoietic Cell Transplantation. Front Immunol 12:634435; doi: 10.3389/fimmu.2021.634435 (2021).

Bost P, De Sanctis F, Canè S, Ugel S, Donadello K, Castellucci M, Eyal D, Fiore A, Anselmi C, Barouni RM, Trovato R, Caligola S, Lamolinara A, Iezzi M, Facciotti F, Mazzariol A, Gibellini D, De Nardo P, Tacconelli E, Gottin L, Polati E, Schwikowski B, Amit I & Bronte V: Deciphering the state of immune silence in fatal COVID-19 patients. Nature Communications 12, 1428 (2021).

Cohen YC, Zada M, Wang S-Y, Bornstein C, David E, Moshe A, Li B, Shlomi-Loubaton S, Gatt ME, Gur C, Lavi N, Ganzel C, Luttwak E, Chubar E, Rouvio O, Vaxman I, Pasvolsky O, Ballan M, Tadmor T, Nemets A, Jarchowcky-Dolberg O, Shvetz O, Laiba M, Shpilberg O, Dally N, Avivi I, Weiner A & Amit I: Identification of resistance pathways and therapeutic targets in relapsed multiple myeloma patients through single-cell sequencing. Nature Medicine 27, 491–503 (2021).

Prinz M, Masuda T, Wheeler MA and Quintana FJ: Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation. Annu Rev Immunol 39, 251–77 (2021).

Wieghofer P, Hagemeyer N, Sankowski R, Schlecht A, Staszewski O, Amann L, Gruber M, Koch J, Hausmann A, Zhang P, Boneva S, Masuda T, Hilgendorf I, Goldmann T, Böttcher C, Priller J, Rossi FMV, Lange C and Prinz M: Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single-cell profiling. EMBO J, e105123, doi: 10.15252/embj.2020105123 (2021).

Regen T, Isaac S, Amorim A, Núñez NG, Hauptmann J, Shanmugavadivu A, Klein M, Sankowski R, Mufazalov IA, Yogev N, Huppert J, Wanke F, Witting M, Grill A, Gálvez EJC, Nikolaev A, Blanfeld M, Prinz I, Schmitt-Kopplin P, Strowig T, Reinhardt C, Prinz M, Bopp T, Becher B, Ubeda C, Waisman A: IL-17 controls central nervous system autoimmunity through the intestinal microbiome. Sci Immunol 6, eaaz6563 (2021).

Bauer C, Quante M, Breunis  WB, Regina C, Schneider M, Andrieux  GA, Gorka O, Groß O, Boerries M, Kammerer B, Hettmer S: Lack of Electron Acceptors Contributes to Redox Stress and Growth Arrest in Asparagine-Starved Sarcoma Cell. Cancers (Basel) 13(3):412; doi: 10.3390/cancers13030412 (2021).

Chhatbar C and Prinz M: The roles of microglia in viral encephalitis: from sensome to therapeutic targeting. Cellular & Molecular Immunology, 18, 250–258 (2021).

Kim J-S, Kolesnikov M, Peled-Hajaj S, Scheyltjens I, Xia Y, Trzebanski S, Haimon Z, Shemer A, Lubart A, Van Hove H, Chappell-Maor L, Boura-Halfon S, Movahedi K, Blinder P, Jung S: A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages. Immunity 54(1):176-190.e7; doi: 10.1016/j.immuni.2020.11.007 (2021).

Schroeder P, Rivalan M, Zaqou S, Krüger C, Schüler J, Long M, Meisel A, Winter Y, Kaindl AM, Lehnardt S: Abnormal brain structure and behavior in MyD88-deficient mice. Brain Behav Immun 91:181-193; doi: 10.1016/j.bbi.2020.09.024 (2021).

Berghoff SA, Spieth L, Sun T, Hosang L, Schlaphoff L, Depp C, Düking T, Winchenbach J, Neuber J, Ewers D, Scholz P, van der Meer F, Cantuti-Castelvetri L, Sasmita AO, Meschkat M, Ruhwedel T, Möbius W, Sankowski R, Prinz M, Huitinga I, Sereda MW, Odoardi F, Ischebeck T, Simons M, Stadelmann-Nessler C, Edgar JM, Nave KA, Saher G: Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis. Nat Neurosci 24(1), 47-60. doi: 10.1038/s41593-020-00757-6 (2020).

Cohen M, Giladi A, Raposo C, Zada M, Li B, Ruckh J, Deczkowska A, Mohar B, Shechter R, Lichtenstein RG, Amit I, Schwartz M: Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies. Life Sci Alliance 4(1):e202000907; doi: 10.26508/lsa.202000907(2020).

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