Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors

The Toll family of receptors consists of cell surface TLRs (TLR4/MD-2, TLR1, TLR2, and TLR6) and intracellular TLRs (TLR3, TLR7, TLR8, and TLR9). Cell surface TLRs sense microbial membranes such as lipopolysaccharide or lipopeptides. Recognition by TLRs is the frontline where pathogens and a host try to take the control of immune responses. Bacteria can modulate the structure of a TLR ligand lipid A to subvert host responses. Cell surface TLRs also sense endogenous ligands which are released in tissue damages as danger signals and induce inflammation in infectious and non-infectious condition. The availability of endogenous ligands and the amount of cell surface TLRs are both tightly limited to keep TLR responses sufficient for containment of pathogens without detrimental responses to the host.