Molecular Neuroimmunology

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. TLRs are expressed in microglia as well as in other cells of the CNS including neurons, and recent data indicate that these receptors play a crucial role in various CNS diseases such as stroke, multiple sclerosis, meningitis, and classical neurodegenerative diseases. 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. Our major aim is to determine how and to which extent innate immune responses contribute to neurodegeneration in CNS disorders.

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Ausgewählte Publikationen:

Lehnardt S, Lachance C, Patrizi S, Lefebvre S, Follett PL, Jensen FE, Rosenberg PA, Volpe JJ, Vartanian T

The Toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J Neurosci 2002 Apr; 22(7):2478-2486

Lehnardt S, Massillon L, Follett PL, Jensen FE, Ratan R, Rosenberg PA, Volpe JJ, Vartanian T

Activation of innate immunity in the CNS leads to neurodegeneration through a Toll-Like Receptor4 dependent pathway.
Proc Natl Acad Sci U S A 2003 Jul; 100(14):8514-8519

Lehnardt S, Schott E, Trimbuch T, Laubisch D, Krueger C, Wulczyn G, Nitsch R, Weber JR

Heat shock protein 60 is an endogenous ligand for Toll-like receptor 4 in the CNS: a cause and consequence of neuronal damage.
J Neurosci 2008 Mar; 28(10):2320-31

Lehnardt S

Innate immunity and neuroinflammation in the CNS: The role of microglia in Toll-like receptor-mediated neuronal injury.
Glia 2010 Feb; 58 (3):253-63

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