In an article in the latest issue of Plos Pathogens, INRS professor Simona Stäger and her team show how the parasite Leishmania donovani uses a physiological response to low oxygen levels (hypoxia) to establish a chronic infection.
The parasite behind visceral leishmaniasis causes a chronic inflammation that enlarges the spleen and creates a hypoxic microenvironment. To compensate for the lack of oxygen and ensure their survival, cells adapt by inducing the expression of the transcription factor HIF-1α, the master regulator of the cellular response to hypoxia.
Professor Stäger and her team have demonstrated the effect of this key regulator on the function of monocytes and macrophages during viceral leishmaniasis, the most severe form of a tropical disease that affects millions of people around the world. These cells are the main targets of the parasite L. donovani
"Our lab work demonstrates that HIF-1α plays a key role in the establishment of chronic Leishmania infections by reducing the capacity of monocytes and macrophages to kill the parasite. We also found that HIF-1α gives these cells immunosuppressant properties," explains Professor Stäger.
About the publication
The results of this study are published in an article entitled "HIF-1α is a key regulator in potentiating suppressor activity and limiting the microbiocidal capacity of MDSC-like cells during visceral leishmaniasis," in Plos Pathogens. Akil Hammami, Belma Melda Abidin, Tania Charpentier, Aymeric Fabié, Annie-Pier Duguay, Krista M. Heinonen, and Simona Stäger of INRS-Institut Armand-Frappier participated in this research, which was funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, Fonds de recherche du Québec - Santé, and the Canada Foundation for Innovation. doi: 10.1371/journal.ppat.1006616
Institut national de recherche scientifique (INRS) is a graduate-level research and training university and ranks first in Canada for research intensity (average funding per professor). INRS brings together some 150 professors and close to 800 students and postdoctoral fellows at its four centres in Montreal, Quebec City, Laval, and Varennes. Its basic research is essential to the advancement of science in Quebec and internationally, and its research teams play a key role in the development of concrete solutions to the problems faced by our society.