Antigen export during liver infection of the malaria parasite augments protective immunity.

GEORGINA N. MONTAGNA; MACARENA BEIGIER; MARTINA BECKER; RICHARD KROZECK; STEPHAN KAUFMANN; KAI MATUSCHEWSKI

mBIO

Journal.asm.org

Año: 2014

Protective immunity against preerythrocytic malaria parasite infection is difficult to achieve. Intracellular Plasmodiumparasites likely minimize antigen presentation by surface-expressed major histocompatibility complex class I (MHC-I)molecules on infected cells, yet they actively remodel their host cells by export of parasite factors. Whether exported liver-stageproteins constitute better candidates for MHC-I antigen presentation to CD8 T lymphocytes remains unknown. Here, we systematicallycharacterized the contribution of protein export to the magnitude of antigen-specific T-cell responses against Plasmodiumberghei liver-stage parasites in C57BL/6 mice. We generated transgenic sporozoites that secrete a truncated ovalbumin(OVA) surrogate antigen only in the presence of an amino-terminal protein export element. Immunization with live attenuatedtransgenic sporozoites revealed that antigen export was not critical for CD8 T-cell priming but enhanced CD8 T-cell proliferationin the liver. Upon transfer of antigen-specific CD8 T cells, liver-stage parasites secreting the target protein were eliminatedmore efficiently. We conclude that Plasmodium parasites strictly control protein export during liver infection to minimizeimmune recognition. Strategies that enhance the discharge of parasite proteins into infected hepatocytes could improve the efficacyof candidate preerythrocytic malaria vaccines.