A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium falciparum sporozoites.
Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and invade hepatocytes as a first and obligatory step of the parasite life cycle in man. Hepatocyte invasion involves proteins secreted from parasite vesicles called micronemes, the most characterized being the thrombospondin-related adhesive protein (TRAP). Here we investigated the expression and function of another microneme protein recently identified in Plasmodium falciparum sporozoites, apical membrane antigen 1 (AMA-1). P. falciparum AMA-1 is expressed in sporozoites and is lost after invasion of hepatocytes, and anti-AMA-1 antibodies inhibit sporozoite invasion, suggesting that the protein is involved during invasion of hepatocytes. As observed with TRAP, AMA-1 is initially mostly sequestered within the sporozoite. Upon microneme exocytosis, AMA-1 and TRAP relocate to the sporozoite surface, where they are proteolytically cleaved, resulting in the shedding of soluble fragments. A subset of serine protease inhibitors blocks the processing and shedding of both AMA-1 and TRAP and inhibits sporozoite infectivity, suggesting that interfering with sporozoite proteolytic processing may constitute a valuable strategy to prevent hepatocyte infection.
Silvie
Olivier
O
INSERM U511, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Université Pierre et Marie Curie, 75013 Paris, France. silvie@ext.jussieu.fr
Franetich
Jean-François
JF
Charrin
Stéphanie
S
Mueller
Markus S
MS
Siau
Anthony
A
Bodescot
Myriam
M
Rubinstein
Eric
E
Hannoun
Laurent
L
Charoenvit
Yupin
Y
Kocken
Clemens H
CH
Thomas
Alan W
AW
Van Gemert
Geert-Jan
GJ
Sauerwein
Robert W
RW
Blackman
Michael J
MJ
Anders
Robin F
RF
Pluschke
Gerd
G
Mazier
Dominique
D
D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000378:metabolism*; D034101:Sporozoites / Q000378:metabolism / Q000472:pathogenicity
D000953:Antigens, Protozoan; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; C069428:thrombospondin-related adhesive protein, protozoan