Plasmodium Sporozoite Biology

Abstract

Plasmodium sporozoite transmission is a critical population bottleneck in parasite life-cycle progression and, hence, a target for prophylactic drugs and vaccines. The recent progress of a candidate antisporozoite subunit vaccine formulation to licensure highlights the importance of sporozoite transmission intervention in the malaria control portfolio. Sporozoites colonize mosquito salivary glands, migrate through the skin, penetrate blood vessels, breach the liver sinusoid, and invade hepatocytes. Understanding the molecular and cellular mechanisms that mediate the remarkable sporozoite journey in the invertebrate vector and the vertebrate host can inform evidence-based next-generation drug development programs and immune intervention strategies.

Figure 1.

Sporozoite formation within the oocyst. Transmission electron micrograph showing Plasmodium berghei sporozoites budding from sporoblasts 10 days after the uptake of parasites by the mosquito. On the right image, some selected structures are highlighted. Blue, plasma membrane; yellow, inner membrane complex; green, microtubules; magenta, nascent rhoptries; cyan, nascent micronemes; brown, rootlet fiber; light blue, nucleus. The image is 4 µm wide. (Image courtesy of Mirko Singer and Stefan Hillmer.)

Figure 2.

Sporozoites in the Anopheles vector. (A) A mosquito infected with green fluorescent parasites. Note the green fluorescence of sporozoites secreted with saliva at the front of the proboscis (arrowhead). (B) Sporozoites in the veins of a mosquito wing. Arrowheads point to two sporozoites stuck in the veins and two that are streaked out because of the fast movement of the hemolymph. (C) Sporozoites (arrowheads) within the salivary canal of the proboscis as they are ejected from the mosquito. (Courtesy of Biology of Parasitism course 2015 at the Marine Biological Laboratory, Woods Hole.)

Figure 3.

Shape and subcellular structure of the Plasmodium sporozoite. (A) Schematic showing the cellular organelles and their position and relative size in the Plasmodium sporozoite. PPR, proximal polar ring; Mito, mitochondrion; PM, plasma membrane (blue); ER, endoplasmic reticulum; IMC, inner membrane complex (yellow); NPC, nuclear pore complex; Ap, apicoplast (yellow); MT, microtubules (green); DG, dense granules (brown); Rho, rhoptries (magenta); Mic, micronemes (cyan); APR, apical polar ring (red). Note the single stack Golgi apparatus and the nucleus being associated to the IMC. (B) Scanning electron micrograph of a Plasmodium berghei sporozoite. Sporozoites are an elongated crescent shape and tailored for lasting continuous locomotion and host cell invasion. When deposited on a substrate sporozoites alternate gliding periods with nongliding phases. Sporozoite material that is shed during gliding locomotion marks the trails. (Image from Montagna et al. 2012c; adapted, with permission, from the authors.) (C) Computer tomogram of the apical end of a sporozoite. Highlighted are plasma membrane (blue), inner membrane complex (yellow), microtubules (green), rhoptries (magenta), and micronemes (cyan).

Figure 4.

Sporozoite motility in vitro. (A) Three sporozoites move in a circular fashion with their apical end leading (red arrowheads) at speeds above 1 µm/sec. Their near-perfect circular trajectory is revealed by the maximum intensity projection (0–60). Time between images is indicated in seconds. Scale bar, 10 µm. (B) Reflection interference contrast microscopy reveals the contact points between sporozoites and substrate (dark areas). Arrowheads point to the same positions of a migrating sporozoite. Note that at these positions the dark and bright areas appear and disappear highlighting the dynamic adhesion to the substrate. Time between images is indicated in seconds. Scale bar, 10 µm. (C) Schematic of the sporozoite pellicle with a focus on the core gliding motility machinery.

Figure 5.

Sporozoite migration in vivo. Sporozoite migration after transmission into the dermis. Shown are sporozoites (white) (far left), the tracks of sporozoites migrating for 50 sec (left), sporozoites (yellow) at the start of the movie overlaid by the tracks (red) (center), and tracks over 50 sec (right) and 500 sec (far right) spatially color-coded such that red, green, and blue colors represent different confocal planes 10 μm apart. (Shots taken from movie courtesy of Rogerio Amino, Institut Pasteur, Paris.)