Innate immune response

Signalling in the innate immune response

Invading pathogens are rapidly sensed by the hosts' innate immune system. The molecular mechanisms underlying pathogen detection and the subsequent cellular responses are rapidly being unveiled, but major knowledge gaps still remain. We focus on the initial steps after activation of the Toll-like receptors (TLRs).

Toll-like receptors (TLRs) are transmembrane receptors that recognize pathogen-associated molecular patterns (PAMPs), molecular signatures which are conserved in pathogens, such as lipopolysaccharides of gram-negative bacteria or viral RNA. TLRs play a central role in innate immunity: recognition of specific PAMPs leads to the activation of immune cell responses including phagocytosis, apoptosis, or the production of cytokines or interferons. They function as homo- or heterodimers or possibly as oligomers. They are characterized by the presence of extracellular Leucine Rich Repeats involved in PAMP recognition and intracellular Toll/IL-1 receptor-like (TIR) domains. Ligand-dependent activation of the TLRs leads to a cascade of intracellular protein-protein interactions involving a set of adapter proteins that ultimately leads to the appropriate cellular effects. We combine MAPPIT with mutagenesis and structural data to map the interfaces of protein interactions in the TLR pathway. With FACS- and Array-MAPPIT, we screen for new interaction partners in the TLR signalling pathways.

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