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

ELife
Takashi ImaiHajime Hisaeda

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.

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Citations

Sep 10, 2015·Vaccines·Marie-Ève LebelAlain Lamarre
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Jan 28, 2021·Expert Review of Vaccines·Daniel Fernandez-RuizLynette Beattie
Jul 20, 2021·Seminars in Immunopathology·Lidia Bosurgi, Carla V Rothlin

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Methods Mentioned

BETA
Infection
density gradient centrifugation
flow cytometry

Software Mentioned

FlowJo

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