1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Cytotoxic activities of CD8+ T cells collaborate with macrophages to protect against blood-stage murine malaria

  1. Takashi Imai
  2. Hidekazu Ishida
  3. Kazutomo Suzue
  4. Tomoyo Taniguchi
  5. Hiroko Okada
  6. Chikako Shimokawa
  7. Hajime Hisaeda  Is a corresponding author
  1. Gunma University Graduate School of Medicine, Japan
  2. Otsuka Pharmaceutical Co., Ltd, Japan
  3. RIKEN Center for Integrative Medical Science, Japan
Research Article
  • Cited 35
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Cite this article as: eLife 2015;4:e04232 doi: 10.7554/eLife.04232

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 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 FasL-dependent manner. Malaria parasites infected erythroblasts express 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. T-cell immunoglobulin- and mucin-domain-containing molecule (Tim-4) contributes to the phagocytosis of malaria parasites infected cells as phosphatidylserine receptor. Our findings provide insight into the molecular mechanisms underlying the protective immunity exerted by CD8+ T cells in collaboration with phagocytes.

Article and author information

Author details

  1. Takashi Imai

    Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Hidekazu Ishida

    Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Kazutomo Suzue

    Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Tomoyo Taniguchi

    Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Hiroko Okada

    Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Chikako Shimokawa

    Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Science, Nagasaki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Hajime Hisaeda

    Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan
    For correspondence
    0521773@gmail.com
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All mouse experiments were approved by the Committee for Ethics on Animal Experiments in the Faculty of Medicine, and performed under the control of the Guidelines for Animal Experiments in the Faculty of Medicine, Gunma University and Kyushu University, according to Japanese law (no. 105) and notification (no. 6) of the Government of Japan. No human samples were used in these experiments.

Reviewing Editor

  1. Ronald N Germain, National Institute of Allergy and Infectious Diseases, United States

Publication history

  1. Received: August 2, 2014
  2. Accepted: February 24, 2015
  3. Accepted Manuscript published: March 11, 2015 (version 1)
  4. Version of Record published: March 20, 2015 (version 2)

Copyright

© 2015, Imai et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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