Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition

Abstract

Malaria infection starts with injection of Plasmodium sporozoites by an Anopheles mosquito into the skin of the mammalian host. How sporozoites locate and enter a blood vessel is a critical, but poorly understood process. In this study, we examine sporozoite motility and their interaction with dermal blood vessels, using intravital microscopy in mice. Our data suggest that sporozoites exhibit two types of motility: in regions far from blood vessels, they exhibit ‘avascular motility’, defined by high speed and less confinement, while in the vicinity of blood vessels their motility is more constrained. We find that curvature of sporozoite tracks engaging with vasculature optimizes contact with dermal capillaries. Imaging of sporozoites with mutations in key adhesive proteins highlight the importance of the sporozoite's gliding speed and its ability to modulate adhesive properties for successful exit from the inoculation site.DOI: http://dx.doi.org/10.7554/eLife.07789.001

Microstructured Blood Vessel Surrogates Reveal Structural Tropism of Motile Malaria Parasites

“…[21] Intriguingly, we also found that sporozoites decrease their speed when circling around thinner pillars compared to larger pillars or when gliding in the absence of pillars ( Figure 5B). This could hint towards the existence of a mechanism that slows sporozoites down when they attach to an object with matching curvature, possibly by allowing the formation of adhesion sites on the surface of the object (a pillar in vitro and a blood vessel in vivo).…”

“…[19,20] In vivo experiments analyzing the tracks of many parasites further showed that sporozoites migrate with slightly reduced speed around capillaries compared to their migration in the surrounding tissue. [21] Around blood capillaries they also adapt a more uniform curvature that appears different from the surrounding tissue, where they often change their shape. [21] These observations led us to the hypothesis that sporozoites develop their curvature to select blood vessels of a matching curvature.…”

“…[21] Around blood capillaries they also adapt a more uniform curvature that appears different from the surrounding tissue, where they often change their shape. [21] These observations led us to the hypothesis that sporozoites develop their curvature to select blood vessels of a matching curvature. To test this hypothesis, we sought to generate PDMS pillars of different diameters as simple blood vessel surrogates in order to probe if sporozoites would specifically associate with pillars of a defined curvature even in the absence of molecular cues.…”

Vaccines to Accelerate Malaria Elimination and Eventual Eradication

“…Mutant sporozoites with decreased migratory behavior and motility speed show dramatic reductions in invasion and infectivity, indicating that migration from the inoculation site poses a significant barrier and thus an ideal opportunity for intervention (Hopp et al 2015). Available data indicate that fewer than 100 sporozoites result in hepatocytic infection following the bite of a mosquito (Fig.…”

Pre-erythrocytic Stage of Malaria Infection and the Molecular Targets Available for Interventions

“…Studies show that sporozoites recognize CD31+ blood vessels (Hopp et al, 2015) in their attempt to exit the dermis, suggesting the possibility of developing antibodies targeting this receptor that may inhibit sporozoites exit from the dermis.…”