Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 212, Issue 9, Pages 1391-1403Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20110575
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Funding
- Johns Hopkins Malaria Research Institute
- Bloomberg Family Foundation
- National Institute of Allergy and Infectious Diseases (NIAID) [AI080668]
- National Institutes of Health [RR00052]
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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.
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