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.
Highlights
Through the bite of an infected mosquito, the mammalian host is infected with Plasmodium sporozoites, which migrate through the skin to invade blood vessels
The gliding motility of Plasmodium sporozoites is essential for their infectivity
Within the first 20 min after intradermal inoculation, sporozoites displace with high speed and minimal constraint, which likely maximizes the volume of tissue that is explored by the population of sporozoites
Summary
Through the bite of an infected mosquito, the mammalian host is infected with Plasmodium sporozoites, which migrate through the skin to invade blood vessels. In comparison to fast migrating mammalian cells, such as lymphocytes, which crawl at approximately 0.1 μm/s, sporozoites move at 1–3 μm/s (Amino et al, 2006; Hellmann et al, 2011; Ejigiri et al, 2012). While on two-dimensional substrates in vitro, salivary gland sporozoites glide in a circular pattern. In the dermis, this motion is transformed to a complex non-linear path (Amino et al, 2006; Hellmann et al, 2011)
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