dendritic cells and hepatocytes use distinct pathways to process protective antigen from plasmodium in vivo树突细胞和肝细胞使用不同的途径来处理从疟原虫体内保护性抗原.pdfVIP

Dendritic Cells and Hepatocytes Use Distinct Pathways to Process Protective Antigen from Plasmodium in vivo 1. 1. 1 1¤ 1 Ian A. Cockburn *, Sze-Wah Tse , Andrea J. Radtke , Prakash Srinivasan , Yun-Chi Chen , Photini 2 1 Sinnis , Fidel Zavala * 1Johns Hopkins Malaria Research Institute and Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America, 2 Department of Medical Parasitology, New York University School of Medicine, New York, New York, United States of America Abstract Malaria-protective CD8+ T cells specific for the circumsporozoite (CS) protein are primed by dendritic cells (DCs) after sporozoite injection by infected mosquitoes. The primed cells then eliminate parasite liver stages after recognizing the CS epitopes presented by hepatocytes. To define the in vivo processing of CS by DCs and hepatocytes, we generated parasites carrying a mutant CS protein containing the H-2Kb epitope SIINFEKL, and evaluated the T cell response using transgenic and mutant mice. We determined that in both DCs and hepatocytes CS epitopes must reach the cytosol and use the TAP transporters to access the ER. Furthermore, we used endosomal mutant (3d) and cytochrome c treated mice to address the role of cross-presentation in the priming and effector phases of the T cell response. We determined that in DCs, CS is cross- presented via endosomes while, conversely, in hepatocytes protein must be secreted directly into the cytosol. This suggests that the main ta