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Activation of the host innate immune response depends on specific recognition of conserved microbial signature molecules called pathogen-associated molecular patterns (PAMPs) or the now more widely accepted microbe-associated molecular patterns (MAMPs) because they recognize any microbe regardless of its degree of pathogenicity1. These molecular patterns are highly conserved throughout evolution and are not likely to be mutated because they are essential for the survival of the microbe. Pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) act by specifically recognizing PAMPs. These transmembrane receptors form early barriers against infectious disease and are the first line of innate immune defense. The recognition of a PAMP leads to the binding, engulfment and subsequent destruction of the invading microbe as well as the activation of cell signaling cascades that lead to the inflammatory response and adaptive immunity.
Discovery of TLRs
TLRs are expressed at high levels on immune phagocytic cells such as macrophages and dendritic cells. Phagocytic cells were first identified by the Russian scientist Ilya Mechnikov in 1883 when he observed the ability of starfish larvae to engulf particles introduced to their bodies2. His theory that white blood cells in the human body also had the ability to phagocytose microbes was initially ridiculed by other researchers but was later proven correct. Aspects of innate immunity are found in all multi-cellular organisms including plants and insects3-5 (See Figure 1 for timeline of TLR research).
Figure 1. Timeline of the history of Toll-like receptors (TLRs).