Mikroglia und ZNS-assoziierte Makrophagen

Microglia and CNS associated Macrophages​​​

Image Description: Left: 3D reconstruction of a microglia; Middle: Myeloid cell (IBA1) in close contact with nerve fibers (βIII-Tubulin) in the murine cornea; Right: Human retinal microglia (IBA1) in association with blood vessels (Collagen IV); Images by Peter Wieghofer

Mononuclear phagocytes represent a diverse group of innate myeloid immune cells across all tissues in the body. In the central nervous system (CNS) microglia represent the tissue-resident macrophage population accompanied by other macrophages in CNS-associated tissues.

Complex organs such as the eye consist of distinct compartments, like the retina, the choroid and the cornea. These compartments can be regarded as niches creating a unique environment for specialized macrophage populations inhabiting these tissues. An important feature is the interaction of macrophages with their surrounding cells like neurons, macroglial or endothelial cells that can quickly change under pathological conditions.​

​​​​Our goal is to decipher the complex nature of these macrophages including microglia in health and disease. To reach this goal, we apply up-to-date methods including flow cytometry, confocal microscopy and next generation sequencing approaches. The combination of flow cytometry and microscopy allows the identification of macrophage subpopulations and their validation with spatial resolution in the tissue. Ultimately, the comparison of transgenic mice with human tissue gives us the opportunity to confirm our findings in the human situation and falsify possible inter-species differences at an early stage of research.

Major Research Goals

• Origin and turnover of microglia and CNS-associated macrophages including the eye
• Investigation of disease-associated subpopulations of myeloid cells
• Comparative analyses between mice and human tissue samples

Schlecht A, Zhang P, Wolf J, Thien A, Rosmus D-D, Boneva S, Schlunck G, Lange C & Wieghofer P (2021) Secreted phosphoprotein 1 expression in retinal mononuclear phagocytes links murine to human choroidal neovascularization. Front. Cell Dev. Biol., 28 January 2021

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

Boneva, S., 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., Lange, C. (2020) Transcriptional Profiling Uncovers Human Hyalocytes as a Unique Innate Immune Cell Population. Front Immunol. 11 567274

Brioschi, S., D'Errico, P., Janova, H., Wojcik, S.M., Meyer-Luehmann, M., Rajendran, L., Wieghofer, P., Paolicelli, R.C., Biber, K. (2020) Detection of synaptic proteins in microglia by flow cytometry. Front Mol Neurosci., doi: 10.3389/fnmol.2020.00149

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, C.* (2020) Transcriptomic Characterization of Human Choroidal Neovascular Membranes Identifies Calprotectin as a Novel Biomarker for Patients with Age-related Macular Degeneration. Am J Pathol. 190: 1632-1642

Ajami, B., Samusik, N., Wieghofer, P., Ho, P.P., Crotti, A., Bjornson, Z., Prinz, M., Fantl, W., Nolan, G.P., Steinman, L. (2018) Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models. Nat. Neurosci. 4: 541–551

Goldmann, T.*, Wieghofer, P.*, Jordão, M.J.*, Prutek, F., Hagemeyer, N., Frenzel, K., Staszewski, O., Kierdorf, K., Amann, L., Krueger, M., Locatelli, G., Hochgarner, H., Zeiser, R., Epelman, S., Geissmann, F., Priller, J., Rossi, F., Bechmann, I., Kerschensteiner, M., Linnarsson, S., Jung, S., Prinz, M. (2016). Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat Immunol. 17: 797-805

Wieghofer, P., Knobeloch K.P., Prinz M. (2015). Genetic targeting of microglia. Glia. 63: 1-22

Goldmann, T.*, Wieghofer, P.*, Müller, P.F., Wolf, Y., Varol, D., Yona, S., Brendecke, S.M., Kierdorf, K., Staszewski, O., Datta, M., Luedde, T., Heikenwalder, M., Jung, S.*, Prinz, M.* (2013). A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat. Neurosci. 16: 1618–1626

Funk, N.*, Wieghofer, P.*, Grimm, S., Schaefer, R., Bühring, H.-J., Gasser, T., and Biskup, S. (2013). Characterization of peripheral hematopoietic stem cells and monocytes in Parkinsons disease. Mov. Disord. 28: 392–395

*equally contributing​​​