title: Lipocalin 2 bolsters innate and adaptive immune responses to blood-stage malaria infection by reinforcing host iron metabolism.
abstract: Plasmodium 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.
authors.affiliation: Laboratory of Malaria Immunology, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Aki
authors.initials: A
authors.lastname: Konishi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Masanori
authors.initials: M
authors.lastname: Yagi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ohata
authors.forename: Taiki
authors.initials: T
authors.lastname: Aoshi
authors.forename: Sawako
authors.initials: S
authors.lastname: Itagaki
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Narita
authors.forename: Noha H
authors.initials: NH
authors.lastname: Abdelgelil
authors.forename: Megumi
authors.initials: M
authors.lastname: Inoue
authors.forename: Richard
authors.initials: R
authors.lastname: Culleton
authors.forename: Osamu
authors.initials: O
authors.lastname: Kaneko
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.forename: Cevayir
authors.initials: C
authors.lastname: Coban
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D056704:Adaptive Immunity; D000818:Animals; D004912:Erythrocytes / Q000469:parasitology; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D006706:Homeostasis; D006790:Host-Parasite Interactions; D006801:Humans; D007113:Immunity, Innate; D007501:Iron / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D016780:Malaria, Vivax / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000097:blood / Q000276:immunology / Q000469:parasitology; D010966:Plasmodium vivax / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000378:metabolism*; D045262:Reticulocytosis
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D007501:Iron