CD68 acts as a major gateway for malaria sporozoite liver infection

• Published in: The Journal of experimental medicine Vol. 212; no. 9; pp. 1391 - 1403
• Main Authors: Cha, Sung-Jae, Park, Kiwon, Srinivasan, Prakash, Schindler, Christian W, van Rooijen, Nico, Stins, Monique, Jacobs-Lorena, Marcelo
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 24-08-2015
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - genetics; Antigens, Differentiation, Myelomonocytic - metabolism; Kupffer Cells - metabolism; Kupffer Cells - parasitology; Kupffer Cells - pathology; Liver - metabolism; Liver - parasitology; Liver - pathology; Malaria - genetics; Malaria - metabolism; Malaria - pathology; Male; Mice; Mice, Knockout; Peptide Library; Plasmodium; Plasmodium berghei - metabolism; Rats; Rats, Sprague-Dawley; Sporozoites - metabolism
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20110575

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.