한빛사논문
Abstract
Sung-Jae Cha,1,2 Min-Sik Kim,3 Akhilesh Pandey,3 and Marcelo Jacobs-Lorena1,2
1Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205
2Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205
3McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205
M.-S. Kim’s present address is Dept. of Applied Chemistry, College of Applied Science, Kyung Hee University, Giheung-gu, Yongin-si Gyeonggi-do 17104, Republic of Korea.
Correspondence to Marcelo Jacobs-Lorena
Abstract
Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine.
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