Research fields and Current projects

Our group is active in the field of neuroimmunology and neurodegeneration with the following major areas:
Cellular and molecular mechanisms of immune cell-mediated neuronal injury
Cellular and molecular mechanisms of cell-autonomous neuronal injury
Cellular and molecular mechanisms of CNS infections
Innate immune receptors in CNS development

The role of innate immune receptors in inflammatory neurodegeneration

Co-cultures of neurons (red) and microglia (green). All nuclei are stained blue.

Co-cultures of neurons (red) and microglia (green). All nuclei are stained blue.

The innate immune system responds to infection via highly conserved pattern-recognition receptors including the Toll-like receptors (TLRs) that signal immediate response to invariant structures of pathogens. However, there is increasing evidence that TLRs may play a crucial role not only in regulating immunity against microbial ligands but also in cellular responses to host-derived stimuli: The immune and inflammatory responses can be triggered in the apparent absence of microbial agents. Although the innate immune system is essential for the integrity of the central nervous system (CNS), the consequences of its activation may also be deleterious for the host. Activation of microglia, the major immune cell in the CNS, occurs in essentially all diseases of the CNS and was an early observation of histologists in the late 19th and early 20th centuries. TLRs are expressed in microglia as well as in other cells of the CNS, and recent data indicate that these receptors play a crucial role in various CNS diseases such as stroke, multiple sclerosis, meningitis, and amyotrophic lateral sclerosis. In addition to infectious ligands of TLRs, host-derived ligands may exist in the CNS. Similar to microbial ligands, these CNS cell-derived ligands may activate the resident host defense of the CNS, thereby initiating inflammation and contributing to neuronal damage. To analyze the role of innate immunity in neuronal damage, we make use of various tools including co-culture assays, immunohisto-/cytochemistry, molecular microbiology, protein chemistry, and animal models including cerebral ischemia and experimental meningitis employing various transgenic mice. Our major aim is to determine how and to which extent innate immune responses contribute to neurodegeneration in CNS disorders. Identification of the underlying molecular mechanisms may open the way to the development of new therapeutic strategies

Selected publications

  • Kaul D, Habbel P, Derkow K, Krüger C, Franzoni E, Wulczyn FG, Bereswill S, Nitsch R, Schott E, Veh R, Naumann T, Lehnardt S Expression of Toll-like receptors in the developing brain. PLoS ONE 2012 May 7(5): e37767. Epub 2012 May 30.
  • Lehmann SM, Krüger C, Park B, Derkow K, Rosenberger K, Baumgart J, Trimbuch T, Eom G, Hinz M, Kaul D, Habbel P, Kälin R, Franzoni E, Rybak A, Nguyen D, Veh R, Ninnemann O, Peters O, Nitsch R, Heppner FL, Golenbock DT, Schott E, Ploegh HL, Wulczyn FG, Lehnardt S An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration. Nat Neuroscience 2012 May 20. doi: 10.1038/nn.3113. [Epub ahead of print]
  • Siffrin V, Radbruch H, Glumm R, Niesner R, Paterka M, Herz J, Leuenberger T, Lehmann SM, Luenstedt S, Rinnenthal JL, Laube G, Luche H, Lehnardt S, Fehling HJ, Griesbeck O, Zipp F (2010) In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity 33:424-36.
  • Lehnardt S, Schott E, Trimbuch T, Laubisch D, Krueger C, Wulczyn G, Nitsch R, Weber JR (2008) A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS. J Neurosci  28:2320-31.
  • Lehnardt S, Massillon L, Follett PL, Jensen FE, Ratan R, Rosenberg PA, Volpe JJ, Vartanian T (2003) Activation of innate immunity in the CNS leads to neurodegeneration through a Toll-Like Receptor4 dependent pathway. Proc Natl Acad Sci U S A 100: 8514-19.

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Research database

For more details please use the Charité Öffnet externen Link im aktuellen Fensterresearch database