When we are exposed to infectious (pathogenic) microorganisms, our immune system works to eliminate them. Besides this reactive component, we also have strategies to limit the damage caused by these invading agents, without directly targeting them. This defense strategy is called “disease tolerance” and is a relatively recent topic of research.
Although this is a well-characterized phenomenon in plants, the concept of disease tolerance in animals was not formally introduced until 2007, when Lars Råberg and Andrew Read showed that some mice were more tolerant to the malaria parasite than others, despite being equally capable of getting rid of it. When he stumbled upon these results, Miguel Soares, immunologist and principal investigator at the Instituto Gulbenkian de Ciência (IGC), realized that the studies he had been conducting in malaria and sepsis also pointed towards that direction.
Previously to Råberg and Read’s publication, Miguel had gathered evidence that metabolism reprogramming was determinant in the way we react to threatening situations, whether these are organ transplants or infections. Inclusively, the team led by the researcher demonstrated that the expression of a “protective gene” by the host controlled the pathogenesis of malaria as well as that of sepsis caused by bacterial infections. These findings were in perfect agreement with the existence of mechanisms of disease tolerance in animals.
To further explore this promising subject, Miguel Soares and Thiago Carvalho organized, in 2010, a meeting that brought together more than 25 immunologists, biologists, and ecologists. In this retreat, at the Convent of Arrábida, several researchers of the IGC and other international experts took the first steps towards what could be a new era in the fight against infections.
The principal investigator of the IGC and several other scientists, including Janelle Ayres, from the Salk Institute, David Schneider, from Stanford University, and Ruslan Medzhitov, from Yale School of Medicine, recall now, in an article published in Science Notes, the details of this pioneer meeting and the discussed topics that still to this day shape their research.
According to the attending researchers, in this meeting, it became clear that the organism’s tolerance to pathogenic agents could be as important, if not more so, as the immune system’s functions, in determining disease susceptibility and infection outcome. As such, exploring the interactions between these two defense fronts could transform the way we treat infectious diseases.
Brought together for a common purpose, the researchers agreed to bring this discussion beyond the monastery’s walls and to collaborate to expand and complement their knowledge on this new area of research. And their ideas have already proved fruitful. For Miguel Soares, in particular, understanding these mechanisms has already allowed him to make important advances in the understanding of malaria and sepsis.
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