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Quantitative imaging of Plasmodium transmission from mosquito to mammal


Plasmodium, the parasite that causes malaria, is transmitted by a mosquito into the dermis and must reach the liver before infecting erythrocytes and causing disease. We present here a quantitative, real-time analysis of the fate of parasites transmitted in a rodent system. We show that only a proportion of the parasites enter blood capillaries, whereas others are drained by lymphatics. Lymph sporozoites stop at the proximal lymph node, where most are degraded inside dendritic leucocytes, but some can partially differentiate into exoerythrocytic stages. This previously unrecognized step of the parasite life cycle could influence the immune response of the host, and may have implications for vaccination strategies against the preerythrocytic stages of the parasite.

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Figure 1: Sporozoite motility in the dermis.
Figure 2: Dermis sporozoites invade blood vessels.
Figure 3: Dermis sporozoites invade lymphatic vessels.
Figure 4: Sporozoite fate in the draining lymph node.


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We thank A. Genovesio, C. Zimmer and J.-C. Olivo-Marin for help with tracking analysis, P. Roux for help with confocal microscopy, the members of the Center for Production and Infection of Anopheles of the Pasteur Institute for mosquitoes rearing, B. Boisson for help in RT-PCR and C. Janse for providing PbGFPCON parasites. We are grateful to G. Milon, C. Bourgouin, P. Sinnis, S. Mecheri and F. Zavala for comments on the manuscript. The work was supported by funds from the Pasteur Institute (Strategic project 'Grand Programme Horizontal Anopheles'), the Howard Hughes Medical Institute and the European Commission (FP6 BioMalPar Network of Excellence). R.A. was supported by the Pasteur Institute Grand Programme Horizontal fellowship and F.F. by a Human Frontier Science Program long-term fellowship. R.M. is a Howard Hughes Medical Institute International Scholar.

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Correspondence to Rogerio Amino, Friedrich Frischknecht or Robert Ménard.

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Supplementary information

Supplementary Fig. 1

The number of sporozoites at the site of mosquito bite decreases with time. (PDF 53 kb)

Supplementary Table 1

Lymph sporozoites end their journey in the first draining lymph node. (PDF 19 kb)

Supplementary Movie 1

Sporozoite gliding in the skin. Two time-lapse series showing 200 seconds of sporozoite movement in the dermis of a hairless mouse at 3 minutes and 19 minutes after a single mosquito bite. The maximum projections of the fluorescent signal at the end of the respective time-lapse series show that the sporozoite gliding velocity decreases with time. Image series acquired with an epifluorescent wide-field microscope. (MOV 3296 kb)

Supplementary Movie 2

A sporozoite glides for 114 seconds with high velocity in the dermis, before slowing down upon encountering a blood vessel and invading the blood vessel wall; note the constriction (arrowhead) of the parasite at 282 seconds. After invading the blood vessel, the sporozoite rests several seconds inside the vessel before being taken away with the blood stream between 300 and 306 seconds. The red color represents projected fluorescent signals after injection of fluorescently labeled BSA, which was used to detect blood vessels with the spinning disk confocal microscope (BSA is taken up by endothelial and other dermal cells). The green signal of the sporozoite corresponds to a single confocal plane. Image series acquired with a spinning disk confocal microscope. (MOV 1608 kb)

Supplementary Movie 3

A sporozoite glides in the skin for 106 seconds before slowing down its speed and displaying a moving constriction (arrowhead). From 130 seconds onwards, the sporozoite drifts sideways for several hundred seconds. A second sporozoite (entering the field at 83 seconds) is also seen drifting sideways. The fluorescent signal of the sporozoite corresponds to a single confocal plane. Image series acquired with a spinning disk confocal microscope. (MOV 4761 kb)

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Amino, R., Thiberge, S., Martin, B. et al. Quantitative imaging of Plasmodium transmission from mosquito to mammal. Nat Med 12, 220–224 (2006).

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