Cytotoxic activities of CD8+ T cells collaborate with macrophages to protect against blood-stage murine malaria

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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.

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Takashi Imai

Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan

Competing interests
The authors declare that no competing interests exist.
Hidekazu Ishida

Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan

Competing interests
The authors declare that no competing interests exist.
Kazutomo Suzue

Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan

Competing interests
The authors declare that no competing interests exist.
Tomoyo Taniguchi

Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan

Competing interests
The authors declare that no competing interests exist.
Hiroko Okada

Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan

Competing interests
The authors declare that no competing interests exist.
Chikako Shimokawa

Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Science, Nagasaki, Japan

Competing interests
The authors declare that no competing interests exist.
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.

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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.