title: Cytotoxic activities of CD8⁺ T cells collaborate with macrophages to protect against blood-stage murine malaria.
abstract: The protective immunity afforded by CD8(+) T cells against blood-stage malaria remains controversial because no MHC class I molecules are displayed on parasite-infected human erythrocytes. We recently reported that rodent malaria parasites infect erythroblasts that express major histocompatibility complex (MHC) class I antigens, which are recognized by CD8(+) T cells. In this study, we demonstrate that the cytotoxic activity of CD8(+) T cells contributes to the protection of mice against blood-stage malaria in a Fas ligand (FasL)-dependent manner. Erythroblasts infected with malarial parasites express the death receptor Fas. CD8(+) T cells induce the externalization of phosphatidylserine (PS) on the infected erythroblasts in a cell-to-cell contact-dependent manner. PS enhances the engulfment of the infected erythroid cells by phagocytes. As a PS receptor, T-cell immunoglobulin-domain and mucin-domain-containing molecule 4 (Tim-4) contributes to the phagocytosis of malaria-parasite-infected cells. Our findings provide insight into the molecular mechanisms underlying the protective immunity exerted by CD8(+) T cells in collaboration with phagocytes.
authors.affiliation: Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
authors.affiliation: Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Suzue
authors.affiliation: Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Taniguchi
authors.affiliation: Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Okada
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Science, Yokohama, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Shimokawa
authors.affiliation: Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Hisaeda
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004900:Erythroblasts / Q000276:immunology / Q000469:parasitology; D005089:Exocytosis / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010587:Phagocytosis / Q000276:immunology; D010718:Phosphatidylserines / Q000276:immunology / Q000378:metabolism; D010967:Plasmodium yoelii / Q000276:immunology* / Q000502:physiology
chemical_list: D053222:Fas Ligand Protein; D008565:Membrane Proteins; D010718:Phosphatidylserines; C500399:TIM-4 protein, mouse
keywords: +; erythroblast; immunology; infectious disease; malaria; microbiology; mouse