introduction
the Fee-Like Recipients (Where from Toll-like receptors Where from TLR’s) belong to the large family of PRRs (1-3) (pattern recognition receptors).
Structure of the human TLR3)
As such, they interfere with the mechanisms of innate immunity by recognizing “conserved molecular patterns” in many pathogens.
These patterns, known as PAMPs (Pathogen-Associated Molecular Patterns), are of very different origins (bacteria, viruses (A virus is a biological entity that needs a host cell that uses it…), parasites) and of diverse nature (protein, ose (The oses (or monosaccharides) are the monomers of carbohydrates. They are not hydrolyzable….), acid (An acid is a chemical compound generally defined by its reactions…)nucleic).
phylogeny
TLRs are found in mammals and many vertebrates (vertebrates form a subdivision of the animal kingdom. This taxon, which in its…) (osseous or cartilaginous fish, amphibians, reptiles and birds), but also in invertebrates and in some plants in slightly different structural forms .
So, from a (graphic) point of view (sight is the sense that makes it possible to observe and analyze the environment by receiving and…), the TLRs seem to be one of the oldest components of the immune system ( The immune system of an organism is a coordinated set of elements of …) and would have occurred even before the separation (generally the word separation denotes an action consisting in separating some …) between animals and plants.
discovery
The name TLR comes from homology with a family of molecules found in Drosophila (Drosophila (from Greek drosos: dew and philos: who loves) is an insect…) Drosophila melanogaster, whose main member is Toll. (“Toll” means “amazing” or “cool” in German). In Drosophila, Toll was originally identified as a gene (A gene is a deoxyribonucleic acid (DNA) sequence specifying the…) important during embryogenesis and particularly during the establishment of the dorsoventral axis (4). In 1996, Jules Hoffmann and his team showed that Toll is also involved in antifungal immunity in Drosophila (5).
At the time of this discovery, TLRs in mammals were known thanks to the chromosomal identification of TIL (now called TLR1) by Taguchi’s team in 1996 (6). Given what was known about Toll in Drosophila, hypotheses at the time pointed to a role for TIL in mammalian embryonic development. In addition, another molecule (A molecule is an electrically neutral chemical assembly of at least two atoms that …) with an apparent role in mammalian immunity, the interleukin-1 receptor (IL-1R), was identified as early as 1991 by Nick Gay and in particular the homology of the cytoplasmic domain with that of Toll (7).
Charles Janeway and collaborators identify a second TLR paralogue in 1997, which they call “h-Toll” (now TLR4). (8th). They take up Hoffmann’s work and suggest that h-Toll might “activate adaptive immunity” in mammals. The precise function of TLR4 was discovered in 1998 by Bruce Beutler’s group, who used a genetic technique called “positional cloning” to prove the role of TLR4 as a receptor for bacterial lipopolysaccharide (also known as “endotoxin” or LPS). By then, LPS had been known for its potent inflammatory and immunomodulatory effects for over a hundred years. By examining the consequences of the loss of this TLR in mice (The term mouse is an ambiguous common name that can refer to French speakers before…) invalidated for TLR4, Beutler concluded that the specificity of recognition from LPS through TLR4. This observation (observation is the act of attentively observing phenomena without the will to them…) strongly suggests that in mammals each TLR might recognize a very specific molecule indicative of an ongoing infection.
It now appears that this claim was correct and that TLRs represent key proteins in mammals that allow them to detect infection and trigger the immune response.