The innate immune system promotes and guides adaptive immune responses, particularly against intracellular pathogens, through the recognition of pathogen-associated molecular patterns. An improved understanding of the functional properties of this system, its key ligand-receptor systems and their signaling cascades is a pre-requisite for the development of new strategies for immune intervention. Toll-like receptors (TLRs) represent the best-characterized family of pattern-recognition receptors. Their engagement triggers overlapping, yet distinct patterns of gene expression. This review will be mainly focused on TLR2 and the signaling/effector events triggered by its activation. TLR2 ligands, such as lipoproteins from different bacterial species, were shown to promote the expression of pro-inflammatory genes, and to lead to the activation and maturation of dendritic cells. A synthetic analog of the Mycoplasma-derived macrophage activating lipopeptide MALP-2 is an agonist of the heterodimer TLR2/TLR6. MALP-2 is a potent mucosal adjuvant, as well as an efficient immune stimulator for tumor surveillance and wound healing. TLR signaling is regulated at multiple levels, to avoid immune pathological reactions. These aspects will be dissected in this review. The understanding of the interplay between activating and inhibiting cascades might facilitate the design of novel approaches based on TLR signaling to prevent and treat human disease.
Keywords: toll-like receptor, tlr, innate immunity, adaptive immunity, malp, immune modulation
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