A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium falciparum sporozoites |
| |
Authors: | Silvie Olivier Franetich Jean-François Charrin Stéphanie Mueller Markus S Siau Anthony Bodescot Myriam Rubinstein Eric Hannoun Laurent Charoenvit Yupin Kocken Clemens H Thomas Alan W Van Gemert Geert-Jan Sauerwein Robert W Blackman Michael J Anders Robin F Pluschke Gerd Mazier Dominique |
| |
Affiliation: | 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 |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|