The TLR Discovery

The implication of Toll-like receptors in innate immunity (Nobel Prize 2011) is part of a vast body of research that changed our view on the immune system. This includes conceptual advances such as (i) the concept of pattern-recognition which defines innate immune receptors recognizing molecules specific of infectious agents, or (ii) the two-signal model which states that most B and T cell adaptive immune responses are triggered by the simultaneous presence of non-self (antigen) and of a danger signals. The progress also includes an extensive molecular and genetic dissection of many sensing receptors and their downstream pathways, thus revealing the complexity of innate immune responses. The steps leading to this discovery involved many fields of research, notably NF-kappaB and IL-1 signaling in mammalian cell culture, genetic dissection of the Toll pathway in Drosophila, invertebrate and plant immunology, mouse genetics, adjuvant and microbial cell wall biochemistry…

The discovery of Toll-like-receptors was like the fall of a ripe fruit, implying many laboratories working in different locations in the world, with different lines of research. Credit allocations and recognition obey to the logic of the Matthew effect where prize and recognition go to few members, generally the most visible of the community, with a distortion of reality.

I have collected a number of accounts of first authors involved in this discovery to decipher the paths which led to the identification of Toll-like-receptors (work in progress). The aim was to clarify when they started their research, on which basis, what were the critical steps and how were their results published or released to the community. There are still some grey zones with conflicting testimonies but otherwise there is evidence for a collective progress with no clear-cut critical step to be identified. If you have been involved in this discovery, or if you are a witness, you are welcome to send me any information.

Below is a text that I wrote at the time of the 2011 Nobel Prize award, relating my relation with my former supervisor. This narrative, written with a certain naivety, does not take into account all the new information I have obtained over the years by discussing with other players of the Toll adventure. Nevertheless, I still believe it to be correct concerning the Drosophila immunity part and so far it has never been contradicted. (2011)