Guardians of neuroimmunity – Toll-like receptors and their RNA ligands

Abstract

Abstract RNA-sensing Toll-like receptors (TLRs) are mostly associated with the recognition of viruses. However, over the last years it has become clear that the function and relevance of these receptors are far more complex. They are essential for the recognition of bacteria, fungi and parasites, leading to transcriptional activation of central nervous system (CNS) resident and invading myeloid cells during infectious meningitis and encephalitis. Moreover, host-derived RNA species interact with TLRs. Injured CNS neurons release small RNAs, e. g. microRNAs, into the extracellular space. Neighboring neurons and microglia take up these RNA molecules via the endosomal route, which provides the opportunity for activation of endosomal TLRs. This process contributes to neuroinflammation and further neuronal injury, thus closing the vicious cycle of CNS damage, as it may occur in numerous CNS disorders including neurodegenerative diseases.