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.
© 2016 Cha et al.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Protozoan / immunology
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Antigens, CD / metabolism
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Antigens, Differentiation, Myelomonocytic / metabolism
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Cell Line
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Cell Membrane / enzymology*
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Conserved Sequence
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Glyceraldehyde-3-Phosphate Dehydrogenases / chemistry
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Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism*
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Humans
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Kupffer Cells / parasitology
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Kupffer Cells / pathology
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Ligands
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Liver / parasitology*
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Liver / pathology*
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Malaria / immunology
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Malaria / parasitology*
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Malaria Vaccines / immunology
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Mice, Knockout
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Peptides / chemistry
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Peptides / immunology
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Plasmodium berghei / immunology
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Plasmodium berghei / pathogenicity*
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Protein Binding
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Rats
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Sporozoites / enzymology*
Substances
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Antibodies, Protozoan
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD68 antigen, human
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Ligands
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Malaria Vaccines
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Peptides
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Glyceraldehyde-3-Phosphate Dehydrogenases
Associated data
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RefSeq/.1
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RefSeq/NM_001031638