High speed, three-dimensional imaging reveals chemotactic behavior specific to human-infective Leishmania parasites

Abstract

Cellular motility is an ancient eukaryotic trait, ubiquitous across phyla with roles in predator avoidance, resource access and competition. Flagellar-dependent motility is seen in a variety of parasitic protozoans and morphological changes in flagellar structure and function have been qualitatively described during differentiation. However, whether the dynamics of flagellar motion vary across lifecycle stages and whether such changes serve to facilitate human infection is not known. Here we used holographic video microscopy to study the pattern of motility in insect midgut forms of Leishmania (procyclic promastigotes; PCF) and differentiated human infective metacyclic promastigotes (META). We discovered that PCF swim in a slow, corkscrew motion around a gently curving axis while META display run and tumble behaviour in the absence of stimulus, reminiscent of bacterial behaviour. In addition, we demonstrate that META specifically respond to a macrophage-derived stimulus, modifying swimming direction and speed to target host immune cells. Thus, the motility strategy employed by Leishmania appears as a random search that is replaced with a ballistic swimming motion in the presence of an immunological stimulus. These findings shed unique insights into how flagellar motion adapts to the particular needs of the parasite at different times in its lifecycle and define a new pre-adaptation for infection of the human host.