title: CD68 acts as a major gateway for malaria sporozoite liver infection.
abstract: After being delivered by the bite from an infected mosquito, Plasmodium sporozoites enter the blood circulation and infect the liver. Previous evidence suggests that Kupffer cells, a macrophage-like component of the liver blood vessel lining, are traversed by sporozoites to initiate liver invasion. However, the molecular determinants of sporozoite-Kupffer cell interactions are unknown. Understanding the molecular basis for this specific recognition may lead to novel therapeutic strategies to control malaria. Using a phage display library screen, we identified a peptide, P39, that strongly binds to the Kupffer cell surface and, importantly, inhibits sporozoite Kupffer cell entry. Furthermore, we determined that P39 binds to CD68, a putative receptor for sporozoite invasion of Kupffer cells that acts as a gateway for malaria infection of the liver.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health; and Department of Neurology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21205 W. Harry Feinstone Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health; and Department of Neurology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: Sung-Jae
authors.initials: SJ
authors.lastname: Cha
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health; and Department of Neurology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21205 W. Harry Feinstone Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health; and Department of Neurology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: Kiwon
authors.initials: K
authors.lastname: Park
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Prakash
authors.initials: P
authors.lastname: Srinivasan
authors.affiliation: Department of Microbiology and Immunology and Department of Medicine, Columbia University, New York, NY 10032 Department of Microbiology and Immunology and Department of Medicine, Columbia University, New York, NY 10032.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Schindler
authors.affiliation: Department of Molecular Cell Biology and Immunology, VUmc, 1081 BT Amsterdam, Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health; and Department of Neurology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: Monique
authors.initials: M
authors.lastname: Stins
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health; and Department of Neurology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21205 W. Harry Feinstone Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health; and Department of Neurology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21205 mlorena@jhsph.edu.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Jacobs-Lorena
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008288:Malaria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019151:Peptide Library; D010962:Plasmodium berghei / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D034101:Sporozoites / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019151:Peptide Library; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C539355:CD68 protein, rat