Lipocalin 2 bolsters innate and adaptive immune responses to blood-stage malaria infection by reinforcing host iron metabolism
| Autor: | Yukiko Fujita, Richard Culleton, Sawako Itagaki, Megumi Inoue, Hong Zhao, Atsushi Nakagawa, Masanori Yagi, Toshihiro Horii, Ken Ishii, Osamu Kaneko, Taiki Aoshi, Shintaro Sato, Keiichi Ohata, Aki Konishi, Shizuo Akira, Cevayir Coban, Hirotaka Narita, Noha H. Abdelgelil |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Erythrocytes Reticulocytosis Anemia Iron Parasitemia Biology Adaptive Immunity Microbiology Plasmodium Host-Parasite Interactions Mice Immune system Lipocalin-2 Immunity Virology Immunology and Microbiology(all) Proto-Oncogene Proteins parasitic diseases medicine Malaria Vivax Macrophage Animals Homeostasis Humans Molecular Biology Mice Knockout Mice Inbred BALB C Macrophages Plasmodium yoelii medicine.disease biology.organism_classification Acquired immune system Immunity Innate Lipocalins Malaria Mice Inbred C57BL Immunology Parasitology medicine.symptom Plasmodium vivax Acute-Phase Proteins Granulocytes |
| Zdroj: | Cell hostmicrobe. 12(5) |
| ISSN: | 1934-6069 |
| Popis: | SummaryPlasmodium parasites multiply within host erythrocytes, which contain high levels of iron, and parasite egress from these cells results in iron release and host anemia. Although Plasmodium requires host iron for replication, how host iron homeostasis and responses to these fluxes affect Plasmodium infection are incompletely understood. We determined that Lipocalin 2 (Lcn2), a host protein that sequesters iron, is abundantly secreted during human (P. vivax) and mouse (P. yoeliiNL) blood-stage malaria infections and is essential to control P. yoeliiNL parasitemia, anemia, and host survival. During infection, Lcn2 bolsters both host macrophage function and granulocyte recruitment and limits reticulocytosis, or the expansion of immature erythrocytes, which are the preferred target cell of P. yoeliiNL. Additionally, a chronic iron imbalance due to Lcn2 deficiency results in impaired adaptive immune responses against Plasmodium parasites. Thus, Lcn2 exerts antiparasitic effects by maintaining iron homeostasis and promoting innate and adaptive immune responses. |
| Databáze: | OpenAIRE |
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