How pathogens modulate over time the evolution of our immune system
Through a study of human genetics in different populations worldwide, French researchers (from the Pasteur Institute and CNRS) have discovered how pathogens may vary over time the evolution of our immune system. It is as if, unlike viruses, bacteria, fungi and parasites seem to have allowed the introduction of mutations in the genes of certain immune system proteins, thus allowing greater genetic variability. In some cases, these mutations could even be an advantage, giving the human host more resistant to infectious diseases such as leprosy or tuberculosis. The researchers published their discovery in the online journal PLoS Genetics dated July 17, 2009 (reference Article 1 below)

TLR: Toll-like receptors
The results of this study illustrate the influence relationships between humans and pathogens. Scientists are studying this genetic variability of ten proteins innate immune system, the first line of defense against these agents which attack our body. These proteins are a family of receptors called TLR (for Toll-like receptors) and are responsible for recognizing pathogens to trigger an immune response and eliminate them.

The researchers' work showed a strong similarity among different populations in the world of genes TLR recognizing viruses: mutations are very rare, and the level of sequence conservation of these genes is extreme. Viruses have therefore exercised over time a very strong selective pressure on these proteins, preventing them to evolve genetically. Conversely, genes TLR recognizing bacteria, fungi or parasites show more variability: it seems possible that mutations accumulate without it being critical to the organization. This suggests that the role of these proteins is not essential.

Disadvantageous and advantageous mutations
This research corroborates the observations showing that the few known mutations affecting the genes of TLRs "virus" are the source of rare and serious diseases. This is the case for a mutation that affects the gene TLR 3, which was previously identified as responsible for encephalitis. Mutations affecting the genes of other types of TRL, in turn, cause or contribute to infectious disease less severe and more frequent. One of the mutations affecting TLR gene 6 is such to cause a predisposition to asthma in children.

Through this study, scientists have also been shown that a mutation affecting the receptor TLR1, designed to identify bacteria, could be an advantage! Found in two out of five in Europe, this mutation has the effect of preventing the expression of this receptor on the cell surface and therefore reduce from 40 to 60% of the inflammatory response. In previous studies, this mutation has been associated with even greater strength vis-a-vis leprosy and tuberculosis.

The evolutionary approach to this study brings an original perspective on the issue of Human Relations / pathogens. From the direct analysis of genetic sequences, it opens paths to explore a clinical perspective, immunological and epidemiological research to better understand the susceptibility to certain diseases.


The Toll-like receptors
The Toll-like receptors derive their name from the What do these protein homology with a family of molecules found in the fly Drosophila (Drosophila melanogaster), whose main member is Toll. (Toll is a German word which means amazing, brilliant). In Drosophila, Toll was originally identified as a gene important in embryogenesis, especially during the establishment of the dorsoventral axis. In 1996, Jules Hoffmann and his team (Strasbourg, France) shows that Toll is also involved in the anti-fungal immunity in Drosophila (see reference section 2.)

Article 1: Evolutionary Dynamics of Human Toll-Like Receptors and Their Different Contributions to Host Defense
Authors: Luis B. Barreiro, Meriem Ben-Ali, Helen Quach, Guillaume Laval, Etienne Patin, Joseph K. Pickrell, Christiane Bouchier, Magali Tichit Neyrolles Olivier, Brigitte Gicquel, Judith R. Kidd, Kenneth K. Kidd, Alexander Alcais, Josiane Ragimbeau, Sandra Pellegrini, Laurent Abel, Jean-Laurent Casanova, Lluis Quintana-Murci
Published Journal: PLoS Genetics
DOI: 10.1371/journal.pgen.1000562

Article 2: The dorsoventral regulatory gene cassette Spatzle / Toll / cactus controls the potent antifungal response in Drosophila adults.
Authors: Bruno Lemaitre, Emmanuelle Nicolas, Lydia Michaut, Jean-Marc Reichhart, Jules A Hoffmann
Journal Publication: Cell
DOI: 10.1016/S0092-8674 (00) 80172-5

Source: CNRS, Wikipedia
Photo credit: Stephan Borensztajn


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