Guillermo Arango Duque
Postdoctoral fellow in Cellular Biology
Institut national de la recherche scientifique
Published in: PLOS Pathogens
Leishmania-type parasites cause debilitating diseases around the world. The microorganism is transmitted when an infected phlebotomine insect feeds on a mammal, inoculating the parasite in its promastigote stage. Ingested by the mammal’s immune cells, including its macrophages, the parasite ends up isolated in an organelle known as a phagosome. Normally, the phagosome’s toxic environment enables the macrophages to eliminate the microbes, but the promastigotes find a way to survive and differentiate into amastigotes, which are responsible for disease. To carry out this feat, Leishmania relies on virulence molecules such as the GP63 metalloprotease and lipophosphoglycan. While GP63 deactivates the antimicrobial pathways by cleaving the macrophage’s key proteins, the lipophosphoglycan prevents the phagosome from acquiring its microbicidal properties. Still, these virulence molecules must reach their targets on either side of the cell. Because Leishmania does not inject its effectors through the membrane that surrounds the phagosome, Guillermo Arango Duque assessed whether the components of the macrophage could lead to their redistribution. He found that Leishmania builds on pre-existing secretion mechanisms to force its molecules outside the phagosome. The research sheds light on the way in which Leishmania harnesses the biology of the macrophages and paves the way for new treatments for leishmaniasis.