Cell-passage activity is required for the malarial parasite to cross the liver sinusoidal cell layer.
Liver infection is an obligatory step in malarial transmission, but it remains unclear how the sporozoites gain access to the hepatocytes, which are separated from the circulatory system by the liver sinusoidal cell layer. We found that a novel microneme protein, named sporozoite microneme protein essential for cell traversal (SPECT), is produced by the liver-infective sporozoite of the rodent malaria parasite, Plasmodium berghei. Targeted disruption of the spect gene greatly reduced sporozoite infectivity to the liver. In vitro cell invasion assays revealed that these disruptants can infect hepatocytes normally but completely lack their cell passage ability. Their apparent liver infectivity was, however, restored by depletion of Kupffer cells, hepatic macrophages included in the sinusoidal cell layer. These results show that malarial sporozoites access hepatocytes through the liver sinusoidal cell layer by cell traversal motility mediated by SPECT and strongly suggest that Kupffer cells are main routes for this passage. Our findings may open the way for novel malaria transmission-blocking strategies that target molecules involved in sporozoite migration to the hepatocyte.
Ishino
Tomoko
T
Mie University School of Medicine, Mie, Japan.
Yano
Kazuhiko
K
Chinzei
Yasuo
Y
Yuda
Masao
M
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D020224:Expressed Sequence Tags; D005260:Female; D006367:HeLa Cells; D022781:Hepatocytes / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D007728:Kupffer Cells / Q000469:parasitology; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000469:parasitology*; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D010962:Plasmodium berghei / Q000378:metabolism*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D034101:Sporozoites / Q000378:metabolism
D018076:DNA, Complementary; D015800:Protozoan Proteins; C510153:SPECT protein, Plasmodium berghei