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Centre de recherche
Tuesday, January 12 2016
Press release

Innate immune defences triggered by unsuspected mechanism

Loss of methylation occurs rapidly after infection

MONTREAL, January 12, 2016 – To the surprise of researchers in immunology and genetics, a previously unsuspected mechanism is activated in the presence of pathogens after only a few hours. “In the hours following an attack by bacteria, we observed the activation of thousands of genes in the cells of the innate immune system (the one we are born with) and the triggering of its immune defences,” said Luis Barreiro, professor at University of Montreal and researcher at its affiliated children research hospital CHU Sainte-Justine. “We were surprised that a bacterial infection caused thousands of changes in DNA methylation, considering that this epigenetic marker was thought to be stable and non-reactive to environmental perturbations,” he added.

To reach this conclusion, the researcher and his team infected dendritic cells, which are part of the innate immune system, with a live strain of Mycobacterium tuberculosis (the pathogen that causes tuberculosis in humans). "In addition to observing thousands of DNA methylation changes very quickly after infection, there was a significant loss of methylation, which was strongly linked to the activation of neighbouring genes," said the principal investigator of the study.

Another surprising fact was that the reaction took place in dendritic cells, which do not proliferate. “Normally demethylation occurs during cell division. The rapid triggering of this epigenetic change in cells that do not divide surprised us,” said Alain Pacis, a doctoral student and first author of the study. “We must further explore the mechanism that makes this process possible.”

Recent studies suggest that after first encountering a pathogen or other immune stimuli, innate immune cells keep the attack in memory to respond more effectively and more rapidly to future attacks, much like the adaptive immune system. According to Barreiro, the ability of these cells to remember past attacks can be explained by the lasting epigenetic changes that occur during the first infection. "Several lines of evidence let us believe that the innate immune system also has immunological memory, and that the demethylation of DNA may play an important role in the development of such memory. This is another avenue that needs to be explored.”

Much remains to be done to explain the mysteries surrounding DNA methylation and the mechanisms by which it regulates the innate immune system and gives it a certain memory. Nevertheless, this discovery sheds new light on how to approach the development of vaccines, in particular, by further considering the role of various epigenetic perturbations in triggering the immune response.

About the study

The article "Bacterial infection remodels the DNA methylation landscape of human dendritic cells" was published in the journal Genome Research. Luis Barreiro, PhD, is a researcher at CHU Sainte-Justine and an assistant professor in the Department of Pediatrics, University of Montreal. He has received financial support from the Canadian Institutes of Health Research (CIHR), the Human Frontiers Science Program, and the Canadian Research Chairs (CRC) program. Alain Pacis is a doctoral student in Bioinformatics at the University of Montreal.

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About the CHU Sainte-Justine Research Center

CHU Sainte-Justine Research Center is a leading mother-child research institution affiliated with Université de Montréal. It brings together more than 200 research investigators, including over 90 clinician-scientists, as well as 360 graduate and postgraduate students focused on finding innovative prevention means, faster and less invasive treatments, as well as personalized approaches to medicine. The Center is part of CHU Sainte-Justine, which is the largest mother-child center in Canada and second most important pediatric center in North America. More on research.chusj.org

 

Source
CHU Sainte-Justine
Contact

Marise Daigle, CHU Sainte-Justine Research Center

marise.daigle@recherche-ste-justine.qc.ca

For information

Julie Cordeau-Gazaille, University of Montreal (officially Université de Montréal)

514-343-6796

j.cordeau-gazaille@umontreal.ca

Persons mentioned in the text
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Updated on 1/12/2016
Created on 1/12/2016
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